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developmental and stem cell biologists

April in preprints

Posted by , on 5 May 2021

Welcome to our monthly trawl for developmental biology (and related) preprints.

The preprints this month are hosted on bioRxivarXiv and preprints.org – use these links to get to the section you want.

Developmental biology

Cell Biology

Modelling

Reviews

Tools & Resources

Research practice & education

Developmental biology

| Patterning & signalling

Sox8 is sufficient to reprogram ectoderm into ear vesicles and associated neurons
Ailin Leticia Buzzi, Jingchen Chen, Alexandre Thiery, Julien Delile, Andrea Streit

Human gastruloids from Liu, et al.

Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids
Lizhong Liu, Anastasiia Nemashkalo, Ji Yoon Jung, Sapna Chhabra, M. Cecilia Guerra, Idse Heemserk, Aryeh Warmflash

“Neighborhood watch” model: embryonic epiblast cells assess positional information in relation to their neighbors
Hyung Chul Lee, Cato Hastings, Nidia M.M. Oliveira, Rubén Pérez-Carrasco, Karen M. Page, Lewis Wolpert, Claudio D. Stern

Zebrafish flanks from Ma, et al.

Local signaling specifies tissue-resident fibroblasts from multipotent sclerotome progenitors in zebrafish
Roger C. Ma, Katrinka M. Kocha, Peng Huang

P5A-ATPase controls the ER translocation of Wnt in neuronal migration
Tingting Li, Xiaoyan Yang, Zhigang Feng, Wang Nie, Yan Zou

Temporal regulation of green and red cone specification in human retinas and retinal organoids
Sarah E. Hadyniak, Kiara C. Eldred, Boris Brenerman, Katarzyna A. Hussey, Rajiv C. McCoy, Michael E. G. Sauria, James A. Kuchenbecker, Maureen Neitz, Jay Neitz, James Taylor, Robert J. Johnston Jr.

Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states
Xueqing Chen, Mark M. Emerson

The dorsal blastopore lip is a source of signals inducing PCP in the Xenopus neural plate
Pamela Mancini, Olga Ossipova, Sergei Y. Sokol

Mouse embryos from Bora, et al

DDX21 is a p38-MAPK sensitive nucleolar protein necessary for mouse preimplantation embryo development and cell-fate specification
Pablo Bora, Lenka Gahurova, Andrea Hauserova, Martina Stiborova, Rebecca Collier, David Potěšil, Zbyněk Zdráhal, Alexander W. Bruce

Fish fins from Das, et al.

Generation of specialized blood vessels through transdifferentiation of lymphatic endothelial cells
Rudra Nayan Das, Ivan Bassi, Yanchao Han, Giuseppina Lambiase, Yaara Tevet, Noga Moshe, Stav Refael Safriel, Julian Nicenboim, Matthias Brueckner, Dana Hirsch, Raya Eilam-Altstadter, Wiebke Herzog, Kenneth D. Poss, Karina Yaniv

Biphasic roles of hedgehog signaling in the production and self-renewal of outer radial glia in the ferret cerebral cortex
Shirui Hou, Wan-Ling Ho, Lei Wang, Bryan Kuo, Jun Young Park, Young-Goo Han

Decoding the porcine developing spatial processing system and production of human entorhinal stellate cell-like cells by a direct programming approach
Tobias Bergmann, Yong Liu, Leo Mogus, Julie Lee, Ulrich Pfisterer, Louis-Francois Handfield, Andrea Asenjo-Martinez, Irene Lisa-Vargas, Stefan E Seemann, Jimmy Tsz Hang Lee, Nikolaos Patikas, Birgitte Rahbek Kornum, Mark Denham, Poul Hyttel, Menno P Witter, Jan Gorodkin, Tune H Pers, Martin Hemberg, Konstantin Khodosevich, Vanessa Jane Hall

ATXN10 is required for embryonic heart development and maintenance of epithelial cell phenotypes in the adult kidney and pancreas
Melissa R. Bentley-Ford, Reagan S. Andersen, Mandy J. Croyle, Courtney J. Haycraft, Kelsey R. Clearman, Jeremy B. Foote, Jeremy F. Reiter, Bradley K. Yoder

ERK3-MK5 signaling regulates myogenic differentiation and muscle regeneration by promoting FoxO3 degradation
Mathilde Soulez, Pierre-Luc Tanguay, Florence Dô, Colin Crist, Junio Dort, Alexey Kotlyarov, Matthias Gaestel, Nicolas A. Dumont, Sylvain Meloche

Wnt-dependent activation of ERK mediates repression of chondrocyte fate during calvarial development
Beatriz Ibarra, Cody Machen, Radhika P. Atit

Per1/Per2-Igf2 axis-mediated circadian regulation of myogenic differentiation
Nobuko Katoku-Kikyo, Ellen Paatela, Daniel L. Houtz, Britney Lee, Dane Munson, Xuerui Wang, Mohammed Hussein, Jasmeet Bhatia, Seunghyun Lim, Ce Yuan, Yoko Asakura, Atsushi Asakura, Nobuaki Kikyo

Extensive structural remodeling of the axonal arbors of parvalbumin basket cells during development
Kristina D. Micheva, Marianna Kiraly, Marc M. Perez, Daniel V. Madison

Dopamine desynchronizes the retinal clock through a melanopsin-dependent regulation of acetylcholine retinal waves during development
Chaimaa Kinane, Hugo Calligaro, Antonin Jandot, Christine Coutanson, Nasser Haddjeri, Mohamed Bennis, Ouria Dkhissi-Benyahya

Fly wing discs from Moore, et al.

Hedgehog pathway members Patched and Costal-2 exhibit differences in overgrowth autonomy in Drosophila melanogaster
Shannon L. Moore, Frank C. Adamini, Erik S. Coopes, Dustin Godoy, Shyra J. Northington, Jordan M. Stewart, Richard L. Tillet, Kayla L. Bieser, Jacob D. Kagey

Role of PARP1 in oligodendrocyte differentiation during developmental myelination and remyelination after myelin damage
Yan Wang, Sheng Zhang, Bokyung Kim, Vanessa L. Hull, Jie Xu, Preeti Prabhu, Maria Gregory, Veronica Martinez-Cerdeno, Xinhua Zhan, Wenbin Deng, Fuzheng Guo

Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish
Taichi Noda, Andreas Blaha, Yoshitaka Fujihara, Krista R. Gert, Chihiro Emori, Victoria E. Deneke, Seiya Oura, Sara Berent, Mayo Kodani, Karin Panser, Luis Enrique Cabrera-Quio, Andrea Pauli, Masahito Ikawa

Regulation of Vg1 biogenesis during mesendoderm induction
P. C. Dave P. Dingal, Adam N. Carte, Tessa G. Montague, Alexander F. Schier

Phenotypic diversity and sensitivity to injury of the pulmonary endothelium during a period of rapid postnatal growth
Fabio Zanini, Xibing Che, Carsten Knutsen, Min Liu, Nina Suresh, Racquel Domingo-Gonzalez, Steve H. Dou, Robert C. Jones, David N. Cornfield, Stephen R. Quake, Cristina M. Alvira

Dynamics and heterogeneity of Erk-induced immediate-early gene expression
Siddhartha G. Jena, Catherine Yu, Jared E. Toettcher

Single cell response landscape of graded Nodal signaling in zebrafish explants
Tao Cheng, Yan-Yi Xing, Yun-Fei Li, Cong Liu, Ying Huang, Ying-Jie Zhang, Sean G. Megason, Peng-Fei Xu

Arf6 is necessary for high level Wingless signalling during Drosophila wing development
Julien Marcetteau, Tamàs Matusek, Frédéric Luton, Pascal P. Thérond

Developmental Circadian Disruption Alters Placental Signaling in Mice
Danielle A. Clarkson-Townsend, Katie L. Bales, Karen E. Hermetz, Amber A. Burt, Machelle T. Pardue, Carmen J. Marsit

Activity-dependent alteration of early myelin ensheathment in a developing sensory circuit
Zahraa Chorghay, David MacFarquhar, Vanessa J. Li, Sarah Aufmkolk, Anne Schohl, Paul W. Wiseman, Ragnhildur Thora Káradóttir, Edward S. Ruthazer

RANKL from Bone Marrow Adipose Lineage Cells Promotes Osteoclast Formation and Bone Loss
Yan Hu, Xiaoqun Li, Xin Zhi, Wei Cong, Biaotong Huang, Huiwen Chen, Yajun Wang, Yinghua Li, Lipeng Wang, Chao Fang, Jiawei Guo, Ying Liu, Jin Cui, Liehu Cao, Weizong Weng, Qirong Zhou, Sicheng Wang, Xiao Chen, Jiacan Su

Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
Xiaodong Li, Patrick J. Gordon, John A. Gaynes, Alexandra W. Fuller, Randy Ringuette, Clayton P. Santiago, Valerie A. Wallace, Seth Blackshaw, Pulin Li, Edward M. Levine

Perivascular cells support folliculogenesis in the developing ovary
Shuyun Li, Bidur Bhandary, Tony DeFalco

Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis
Bidur Bhandary, Anna Heinrich, Sarah J. Potter, Nancy Ratner, Tony DeFalco

Mouse gonads from Li, et al.

Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis
Shu-Yun Li, Xiaowei Gu, Anna Heinrich, Emily G. Hurley, Blanche Capel, Tony DeFalco

Uncoupling of ribosome biogenesis and Tor activation by TRIM-NHL proteins promotes terminal differentiation
Jinghua Gui, Felipe Karam Teixeira

Neuronal Dystroglycan regulates postnatal development of CCK/cannabinoid receptor-1 interneurons
Daniel S. Miller, Kevin M. Wright

Rab11 negatively regulates Wingless preventing JNK mediated apoptosis in Drosophila epithelium during embryonic dorsal closure
Nabarun Nandy, Jagat Kumar Roy

Relish plays a dynamic role in the niche to modulate Drosophila blood progenitor homeostasis in development and infection
Parvathy Ramesh, Nidhi Sharma Dey, Aditya Kanwal, Sudip Mandal, Lolitika Mandal

CSF1R-dependent macrophages control postnatal somatic growth and organ maturation
Sahar Keshvari, Melanie Caruso, Ngari Teakle, Lena Batoon, Anuj Sehgal, Omkar L. Patkar, Michelle Ferrari-Cestari, Cameron E. Snell, Chen Chen, Alex Stevenson, Felicity M. Davis, Stephen J. Bush, Clare Pridans, Kim M. Summers, Allison R. Pettit, Katharine M. Irvine, David A. Hume

Regulation of neurogenesis and gliogenesis by the matricellular protein CCN2 in the mouse retina
Golam Mohiuddin, Genesis Lopez, Jose Sinon, M. Elizabeth Hartnett, Anastasiia Bulakhova, Brahim Chúaqour

Fish fins from Paulissen, et al.

Anatomy and Development of the Pectoral Fin Vascular Network in the Zebrafish
Scott Paulissen, Daniel Castranova, Shlomo Krispin, Margaret Burns, Brant M. Weinstein

longfin causes cis-ectopic expression of the kcnh2a ether-a-go-go K+ channel to autonomously prolong fin outgrowth
Scott Stewart, Heather K. Le Bleu, Gabriel A. Yette, Astra L. Henner, Amy E. Robbins, Joshua A. Braunstein, Kryn Stankunas

Worm embryos from Abbatemarco, et al.

The UBAP2L ortholog PQN-59 contributes to stress granule assembly and development in C. elegans
Simona Abbatemarco, Alexandra Bondaz, Francoise Schwager, Jing Wang, Christopher M Hammell, Monica Gotta

FGF8-mediated signaling regulates tooth developmental pace during odontogenesis
Chensheng Lin, Ningsheng Ruan, Linjun Li, Yibin Chen, Xiaoxiao Hu, YiPing Chen, Xuefeng Hu, Yanding Zhang

Pinhead antagonizes Admp to promote notochord formation
Keiji Itoh, Olga Ossipova, Sergei Y. Sokol

Lung organoids from Hein, et al.

R-SPONDIN2+ Mesenchymal Cells Form the Bud Tip Progenitor Niche During Human Lung Development
Renee F.C. Hein, Joshua H. Wu, Yu-Hwai Tsai, Angeline Wu, Alyssa J. Miller, Emily M. Holloway, Tristan Frum, Ansley S. Conchola, Emmanuelle Szenker-Ravi, Bruno Reversade, Kelley S. Yan, Calvin J. Kuo, Jason R. Spence

Early low-level developmental arsenic exposure impacts mouse hippocampal synaptic function
Karl F.W. Foley, Daniel Barnett, Deborah A. Cory-Slechta, Houhui Xia

Functional connectivity of the developing mouse cortex
Rachel M. Rahn, Lindsey M. Brier, Annie R. Bice, Matthew D. Reisman, Joseph D. Dougherty, Joseph P. Culver

A Positive Regulatory Feedback Loop Between EKLF/ KLF1 and TAL1/SCL Sustaining the Erythropoiesis
Chun-Hao Hung, Yu-Szu Huang, Tung-Liang Lee, Kang-Chung Yang, Yu-Chiau Shyu, Shau-Ching Wen, Mu-Jie Lu, Shinsheng Yuan, Che-Kun James Shen

Glowing worms in Li, et al.

P5A-ATPases control the ER translocation of Wnt for neuronal migration
Tingting Li, Xiaoyan Yang, Zhigang Feng, Wang Nie, Yan Zou

Drp1 SUMO/deSUMOylation by Senp5 isoforms influences ER tubulation and mitochondrial dynamics to regulate brain development
Seiya Yamada, Ayaka Sato, Hiroki Akiyama, Shin-ichi Sakakibara

Foxq2 determines blue cone identity in zebrafish
Yohey Ogawa, Tomoya Shiraki, Yoshitaka Fukada, Daisuke Kojima

Activation of innate immune signalling during development predisposes to inflammatory intestine and shortened lifespan
Kyoko Yamashita, Ayano Oi, Hina Kosakamoto, Toshitaka Yamauchi, Hibiki Kadoguchi, Takayuki Kuraishi, Masayuki Miura, Fumiaki Obata

Colony stimulating factor 1 signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands
Martina Hason, Tereza Mikulasova, Olga Machonova, Antonio Pombinho, Tjakko J van Ham, Uwe Irion, Christiane Nüsslein-Volhard, Petr Bartunek, Ondrej Svoboda

Early construction of the thalamocortical axon pathway requires JNK signaling within the ventral forebrain
Jessica G. Cunningham, James D. Scripter, Stephany A. Nti, Eric S. Tucker

The TNF Egr participates in signaling during cell competition in the absence of a requirement for JNK
Albana Kodra, Claire de la Cova, Aditi Sharma Singh, Laura A. Johnston

R7 photoreceptor axon targeting depends on the relative levels of lost and found expression in R7 and its synaptic partners
Jessica Douthit, Ariel Hairston, Gina Lee, Carolyn A. Morrison, Isabel Holguera, Jessica E. Treisman

The Akt-mTOR pathway drives myelin sheath growth by regulating cap-dependent translation
Karlie N. Fedder-Semmes, Bruce Appel

Local autocrine signaling of IGF1 synthesized and released by CA1 pyramidal neurons regulates plasticity of dendritic spines
Xun Tu, Anant Jain, Helena Decker, Ryohei Yasuda

| Morphogenesis & mechanics

Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues
Guillermo Martínez-Ara, Núria Taberner, Mami Takayama, Elissavet Sandaltzopoulou, Casandra E. Villava, Nozomu Takata, Mototsugu Eiraku, Miki Ebisuya

Adhesion dynamics regulate cell intercalation behaviour in an active tissue
Alexander Nestor-Bergmann, Guy B. Blanchard, Nathan Hervieux, Alexander G. Fletcher, Jocelyn Étienne, Bénédicte Sanson

Tubulin Acetylation Promotes Penetrative Capacity of Cells Undergoing Radial Intercalation
Caitlin Collins, Sun K. Kim, Rosa Ventrella, Jen W. Mitchell, Brian Mitchell

Guidance by followers ensures long-range coordination of cell migration through α-Catenin mechanoperception
Arthur Boutillon, Diego Jahn, Sebastian Gonzalez-Tirado, Joern Starruss, Lutz Brusch, Nicolas B David

What basal membranes can tell us about viscous forces in Drosophila ventral furrow formation
Amanda Nicole Goldner, Konstantin Doubrovinski

Simulated cricket embryos from Riga, et al.

Local density determines nuclear movements during syncytial blastoderm formation in a cricket
Seth Donoughe, Jordan Hoffmann, Taro Nakamura, Chris H. Rycroft, Cassandra G. Extavour

C’ elegans seam cells from Riga, et al.

Caenorhabditis elegans LET-413 Scribble is essential in the epidermis for growth, viability, and directional outgrowth of epithelial seam cells
Amalia Riga, Janine Cravo, Ruben Schmidt, Helena R. Pires, Victoria G. Castiglioni, Sander van den Heuvel, Mike Boxem

Keratin dynamics govern the establishment of the maternal-fetal interface
Wallis Nahaboo, Sema Elif Eski, Marjorie Vermeersch, Bechara Saykali, Daniel Monteyne, Thomas M. Magin, Nicole Schwarz, An Zwijsen, David Perez-Morga, Sumeet Pal Singh, Isabelle Migeotte

Calcium waves facilitate and coordinate the contraction of endfeet actin stress fibers in Drosophila interommatidial cells
Donald F. Ready, Henry C. Chang

Pericyte-derived vitronectin regulates blood-CNS barrier function via integrin signaling
Swathi Ayloo, Christopher Gallego Lazo, Shenghuan Sun, Wei Zhang, Bianxiao Cui, Chenghua Gu

Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration
Maureen C. Lamb, Chathuri P. Kaluarachchi, Thiranjeewa I. Lansakara, Yiling Lan, Alexei V. Tivanski, Tina L. Tootle

SKAP2 as a new regulator of oligodendroglial migration and myelin sheath formation
J Ghelman, L Grewing, F Windener, S Albrecht, A Zarbock, T. Kuhlmann

Fish scales from Aman, et al.

Thyroid hormone regulates abrupt skin morphogenesis during zebrafish postembryonic development
Andrew J. Aman, Margaret Kim, Lauren M. Saunders, David M. Parichy

Light-mediated planar polarization of cone photoreceptor cilia contributes to visual acuity in mammals
Michael Housset, Dominic Filion, Nelson Cortes, Hojatollah Vali, Craig Mandato, Christian Casanova, Michel Cayouette

The Drosophila anterior-posterior axis is polarized by asymmetric myosin activation
Hélène Doerflinger, Vitaly Zimyanin, Daniel St Johnston

A neural progenitor mitotic wave is required for asynchronous axon outgrowth and morphology
Jérôme Lacoste, Hédi Soula, Angélique Burg, Agnès Audibert, Pénélope Darnat, Michel Gho, Sophie Louvet-Vallée

Patterned endogenous activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb
Kaizhen Li, Katherine Figarella, Xin Su, Yury Kovalchuk, Jessika Gorzolka, Jonas J. Neher, Nima Mojtahedi, Nicolas Casadei, Ulrike Hedrich-Klimosch, Olga Garaschuk

Fly follicle cells from Gabbert, et al.

Septins are essential for protrusion and detachment in collective border cell migration
Allison M. Gabbert, James A. Mondo, Joseph P. Campanale, Denise J. Montell

Collective border cell migration requires the zinc transporter Catsup to limit endoplasmic reticulum stress
Xiaoran Guo, Wei Dai, Denise Montell

Prostacyclin as a Negative Regulator of Angiogenesis in the Neurovasculature
Tasha Womack, Jiabing Li, Pavel Govyadinov, David Mayerich, Jason Eriksen

Cell division in tissues enables macrophage infiltration
Maria Akhmanova, Attila Gyoergy, Mikhail Vlasov, Fedor Vlasov, Daniel Krueger, Andrei Akopian, Shamsi Emtenani, Aparna Ratheesh, Stefano De Renzis, Daria E. Siekhaus

Zebrafish heme oxygenase 1a is necessary for normal development and macrophage migration
Kaiming Luo, Masahito Ogawa, Anita Ayer, Warwick J Britton, Roland Stocker, Kazu Kikuchi, Stefan H Oehlers

Optogenetic control of receptors reveals distinct roles for actin- and Cdc42-dependent negative signals in chemotactic signal processing
George R. R. Bell, Esther Rincón, Emel Akdoğan, Sean R. Collins

Somite morphogenesis is required for axial blood vessel formation
Eric Paulissen, Joshua S. Waxman, Benjamin L. Martin

Modulation of endometrial E-Cadherin and N-Cadherin by ovarian steroids and embryonic stimuli
Abhishek Tiwari, Nancy Ashray, Neha Singh, Shipra Sharma, Deepak Modi

Evidence for a Nuclear Role for Drosophila Dlg as a Regulator of the NURF Complex
Katherine A. Sharp, Mark J. Khoury, Frederick Wirtz-Peitz, David Bilder

Visualizing the organization and differentiation of the male-specific nervous system of C. elegans
Tessa Tekieli, Eviatar Yemini, Amin Nejatbakhsh, Erdem Varol, Robert W. Fernandez, Neda Masoudi, Liam Paninski, Oliver Hobert

The extracellular matrix controls stem cell specification and tissue morphology in the developing and adult gut
R. Ramadan, S. van Neerven, VM. Wouters, T. Martins Garcia, V. Muncan, OD. Franklin, M. Battle, KS. Carlson, J. Leach, OJ. Sansom, L. Vermeulen, JP. Medema, DJ. Huels

What basal membranes can tell us about viscous forces in Drosophila ventral furrow formation
Amanda N. Goldner, Konstantin Doubrovinski

On the mechanical regulation of epithelial tissue homeostasis
Sara Kaliman, Maxime Hubert, Carina Wollnik, Lovro Nuić, Damir Vurnek, Simone Gehrer, Jakov Lovrić, Diana Dudziak, Florian Rehfeldt, Ana-Sunčana Smith

Self-organization of Tissue Growth by Interfacial Mechanical Interactions in Multi-layered Systems
Tailin Chen, Yan Zhao, Xinbin Zhao, Shukai Li, Jialing Cao, Jing Du, Yanping Cao, Yubo Fan

Pkd1 and Wnt5a genetically interact to control lymphatic vascular morphogenesis in mice
Tevin CY. Chau, Sungmin Baek, Baptiste Coxam, Renae Skoczylas, Maria Rondon-Galeano, Neil I. Bower, Elanor N. Wainwright, Steven SA. Stacker, Helen M. Cooper, Anne K. Lagendijk, Natasha L. Harvey, Mathias François, Benjamin M. Hogan

Physical constraints on growth dynamics guide C. elegans developmental trajectories and animal shape
Joy Nyaanga, Christina Goss, Gaotian Zhang, Hannah N. Ahmed, Elliot J. Andersen, Isabella R. Miller, Justine K. Rozenich, Iris L. Swarthout, Jordan A. Vaughn, Erik C. Andersen, Niall M. Mangan, Sasha Shirman

| Genes & genomes

Developmental stage- and site-specific transitions in lineage specification and gene regulatory networks in human hematopoietic stem and progenitor cells
Anindita Roy, Guanlin Wang, Deena Iskander, Sorcha O’Byrne, Natalina Elliott, Jennifer O’Sullivan, Gemma Buck, Elisabeth F. Heuston, Wei Xiong Wen, Alba Rodriguez Meira, Peng Hua, Anastasios Karadimitiris, Adam J Mead, David Bodine, Irene Roberts, Bethan Psaila, Supat Thongjuea

In vivo dissection of a clustered-CTCF domain boundary reveals developmental principles of regulatory insulation
Chiara Anania, Rafael D. Acemel, Johanna Jedamzick, Adriano Bolondi, Giulia Cova, Norbert Brieske, Ralf Kühn, Lars Wittler, Francisca M. Real, Darío G. Lupiáñez

Maternal and zygotic factors sequentially shape the tissue regionalization of chromatin landscapes in early vertebrate embryos
Kitt D. Paraiso, Ira L. Blitz, Ken W.Y. Cho

Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development
Erica Bresciani, Blake Carrington, Kai Yu, Erika M. Kim, Tao Zhen, Victoria Sanchez Guzman, Elizabeth Broadbridge, Kevin Bishop, Martha Kirby, Ursula Harper, Stephen Wincovitch, Stefania Dell’Orso, Vittorio Sartorelli, Raman Sood, Paul Liu

Cells of the human intestinal tract mapped across space and time
R Elmentaite, N Kumasaka, HW King, K Roberts, M Dabrowska, S Pritchard, L Bolt, SF Vieira, L Mamanova, N Huang, I Goh Kai’En, E Stephenson, J Engelbert, RA Botting, A Fleming, E Dann, SN Lisgo, M Katan, S Leonard, TRW Oliver, CE Hook, K Nayak, F Perrone, LS Campos, C Dominguez-Conde, K Polanski, S Van Dongen, M Patel, MD Morgan, JC Marioni, OA Bayraktar, KB Meyer, M Zilbauer, H Uhlig, MR Clatworthy, KT Mahbubani, K Saeb Parsy, M Haniffa, KR James, SA Teichmann

Temporal single-cell transcriptomes of zebrafish spinal cord pMN progenitors reveal distinct neuronal and glial progenitor populations
Kayt Scott, Rebecca O’Rourke, Caitlin Winkler, Christina A Kearns, Bruce Appel

Dynamics of a hepatocyte-cholangiocyte decision-making gene regulatory network during liver development and regeneration
Sarthak Sahoo, Ashutosh Mishra, Anna Mae Diehl, Mohit Kumar Jolly

Mouse retinas from West, et al.

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity
Emma R. West, Sylvain W. Lapan, ChangHee Lee, Kathrin M. Kajderowicz, Xihao Li, Connie L. Cepko

Chick midbrains from Galton, et al.

A somatic piRNA pathway regulates epithelial-to-mesenchymal transition of chick neural crest cells
Riley Galton, Katalin Fejes-Toth, Marianne E. Bronner

Hnrnpul1 controls transcription, splicing, and modulates skeletal and limb development in vivo
Danielle L Blackwell, Sherri D Fraser, Oana Caluseriu, Claudia Vivori, Amanda V Tyndall, Ryan E Lamont, Jillian S Parboosingh, A Micheil Innes, François P Bernier, Sarah J Childs

Embryo-to-embryo variability in RNAi knockdown efficiency of dKDM5/lid in Drosophila melanogaster
Ashley Albright, Michael Eisen

Fly testes from Gonzales et al.

Maternal Piwi Regulates Primordial Germ Cell Development to Ensure the Fertility of Female Progeny in Drosophila
Lauren E Gonzalez, Xiongzhuo Tang, Haifan Lin

Hematopoietic differentiation is characterized by a transient peak of cell-to-cell gene expression variability in normal and pathological conditions
Charles Dussiau, Agathe Boussaroque, Mathilde Gaillard, Clotilde Bravetti, Laila Zaroili, Camille Knosp, Chloé Friedrich, Philippe Asquier, Lise Willems, Laurent Quint, Didier Bouscary, Michaela Fontenay, Thibault Espinasse, Adriana Plesa, Pierre Sujobert, Olivier Gandrillon, Olivier Kosmider

Blood vessels regulate primary motor neuronal pathfinding in zebrafish via exosome contained microRNA-22
Jiajing Sheng, Jie Gong, Yunwei Shi, Xin Wang, Dong Liu

Illuminati, a novel form of gene expression plasticity in Drosophila neural stem cells
Alix Goupil, Jan Peter Heinen, Fabrizio Rossi, Riham Salame, Carole Pennetier, Anthony Simon, Patricia Skorski, Anxela Lauzao Lauzao, Allison Bardin, Renata Basto, Cayetano Gonzalez

Mouse embryos from Chebrout, et al.

rDNA nascent transcripts promote a unique spatial organization during mouse early development
Martine Chebrout, Maimouna Coura Kone, Habib U. Jan, Marie Cournut, Martine Letheule, Renaud Fleurot, Tiphaine Aguirre-Lavin, Nathalie Peynot, Alice Jouneau, Nathalie Beaujean, Amélie Bonnet-Garnier

Distinct gene expression dynamics in germ line and somatic tissue during ovariole morphogenesis in Drosophila melanogaster
Shreeharsha G Tarikere, Guillem Ylla, Cassandra G. Extavour

delilah, prospero and D-Pax2 constitute a gene regulatory network essential for the development of functional proprioceptors
Adel Avetisyan, Yael Glatt, Maya Cohen, Yael Timerman, Nitay Aspis, Atalya Nachman, Naomi Halachmi, Ella Preger-Ben Noon, Adi Salzberg

Integrative multi-omics analysis reveals conserved hierarchical mechanisms of FOXO3 pioneer-factor activity
Abigail K. Brown, Sun Y. Maybury-Lewis, Ashley E. Webb

The testis-specific transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic program in placental mammals
Deniz M. Özata, Tianxiong Yu, Katharine Cecchini, Haiwei Mou, Amena Arif, Cansu Colpan, Adriano Biasini, Ildar Gaitendinov, Dirk G. de Rooij, Zhiping Weng, Phillip D. Zamore

PRMT5 regulates ovarian follicle development by facilitating Wt1 translation
Min Chen, Fangfang Dong, Min Chen, Zhiming Shen, Haowei Wu, Changhuo Cen, Xiuhong Cui, Shilai Bao, Fei Gao

OTX2 homeoprotein functions in adult choroid plexus
Anabelle Planques, Vanessa Oliveira Moreira, David Benacom, Clémence Bernard, Laurent Jourdren, Corinne Blugeon, Florent Dingli, Vanessa Masson, Damarys Loew, Alain Prochiantz, Ariel A Di Nardo

mTOR driven gene transcription is required for cholesterol production in neurons of the developing cerebral cortex
Martin Schüle, Tamer Butto, Sri Dewi, Laura Schlichtholz, Susanne Strand, Susanne Gerber, Kristina Endres, Susann Schweiger, Jennifer Winter

Sobp modulates Six1 transcriptional activation and is required during craniofacial development
Andre L. P. Tavares, Karyn Jourdeuil, Karen M. Neilson, Himani D. Majumdar, Sally A. Moody

CA1 pyramidal cell diversity is rooted in the time of neurogenesis
Davide Cavalieri, Alexandra Angelova, Anas Islah, Catherine Lopez, Marco Bocchio, Agnès Baude, Rosa Cossart

The piRNA pathway sustains adult neurogenesis by reducing protein synthesis and cellular senescence
C. Gasperini, K. Tuntevski, R. Pelizzoli, A. Lo Van, D. Mangoni, R.M. Cossu, G. Pascarella, P. Bianchini, P. Bielefeld, M. Scarpato, M. Pons-Espinal, R. Sanges, A. Diaspro, C.P. Fitzsimons, P. Carninci, S. Gustincich, D De Pietri Tonelli

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo
Jayson J. Smith, Yutong Xiao, Nithin Parsan, Michael A. Q. Martinez, Frances E. Q. Moore, Nicholas J. Palmisano, Abraham Q. Kohrman, Mana Chandhok Delos Reyes, Rebecca C. Adikes, Taylor N. Medwig-Kinney, Simeiyun Liu, Sydney A. Bracht, Wan Zhang, Kailong Wen, Paschalis Kratsios, David Q. Matus

Spatial expression programs of the intestinal follicle-associated epithelium
Noam Cohen, Hassan Massalha, Shani Ben-Moshe, Adi Egozi, Milena Rozenberg, Keren Bahar Halpern, Shalev Itzkovitz

Joint actions of diverse transcription factor families ensure enhancer selectivity and robust neuron terminal differentiation
Angela Jimeno-Martín, Noemi Daroqui, Erick Sousa, Rebeca Brocal-Ruiz, Miren Maicas, Nuria Flames

Coronary blood vessels from distinct origins converge to equivalent states during mouse and human development
Ragini Phansalkar, Josephine Krieger, Mingming Zhao, Sai Saroja Kolluru, Robert C. Jones, Stephen R Quake, Irving Weissman, Daniel Bernstein, Virginia D. Winn, Gaetano D’Amato, Kristy Red-Horse

Gene expression in mouse and human from Rayon, et al.

Single cell transcriptome profiling of the human developing spinal cord reveals a conserved genetic programme with human specific features
Teresa Rayon, Rory J. Maizels, Christopher Barrington, James Briscoe

Single-cell analysis of early chick hypothalamic development reveals that hypothalamic cells are induced from prethalamic-like progenitors
Dong Won Kim, Elsie Place, Kavitha Chinnaiya, Elizabeth Manning, Changyu Sun, Weina Dai, Kyoji Ohyama, Sarah Burbridge, Marysia Placzek, Seth Blackshaw

Progressive domain segregation in early embryonic development and underlying correlation to genetic and epigenetic changes
Hui Quan, Hao Tian, Sirui Liu, Yue Xue, Yu Zhang, Wei Xie, Yi Qin Gao

Drosophila primary microRNA-8 encodes a microRNA encoded peptide acting in parallel of miR-8
Audrey Montigny, Patrizia Tavormina, Carine Duboe, Hélène San Clémente, Marielle Aguilar, Philippe Valenti, Dominique Lauressergues, Jean-Philippe Combier, Serge Plaza

Parallel functional testing identifies enhancers active in early postnatal mouse brain
Jason T. Lambert, Linda Su-Feher, Karol Cichewicz, Tracy L. Warren, Iva Zdilar, Yurong Wang, Kenneth J. Lim, Jessica Haigh, Sarah J. Morse, Cesar P. Canales, Tyler W. Stradleigh, Erika Castillo, Viktoria Haghani, Spencer Moss, Hannah Parolini, Diana Quintero, Diwash Shrestha, Daniel Vogt, Leah C. Byrne, Alex S. Nord

Neurodevelopment vs. the immune system: complementary contributions of maternally-inherited gene transcripts and proteins to successful egg development in fish
Daniel Żarski, Aurelie Le Cam, Thomas Frohlich, Miwako Kösters, Christophe Klopp, Joanna Nynca, Sławomir Ciesielski, Beata Sarosiek, Katarzyna Dryl, Jerome Montfort, Jarosław Król, Pascal Fontaine, Andrzej Ciereszko, Julien Bobe

A single cell atlas reveals unanticipated cell type complexity in Drosophila ovaries
Maija Slaidina, Selena Gupta, Torsten Banisch, Ruth Lehmann

Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity
Daniel Z. Doyle, Mandy M. Lam, Adel Qalieh, Yaman Qalieh, Alice Sorel, Owen H. Funk, Kenneth Y. Kwan

The DNA-to-cytoplasm ratio broadly activates zygotic gene expression in Xenopus
David Jukam, Rishabh R Kapoor, Aaron F Straight, Jan M. Skotheim

A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis
Elliot T. Martin, Patrick Blatt, Elaine Ngyuen, Roni Lahr, Sangeetha Selvam, Hyun Ah M. Yoon, Tyler Pocchiari, Shamsi Emtenani, Daria E. Siekhaus, Andrea Berman, Gabriele Fuchs, Prashanth Rangan

DNMT3A-dependent DNA methylation is required for spermatogonial stem cells to commit to spermatogenesis
Mathilde Dura, Aurélie Teissandier, Mélanie Armand, Joan Barau, Lorraine Bonneville, Michael Weber, Laura G. Baudrin, Sonia Lameiras, Deborah Bourc’his

A fast Myh super enhancer dictates adult muscle fiber phenotype through competitive interactions with the fast Myh genes
Matthieu Dos Santos, Stéphanie Backer, Frédéric Auradé, Matthew Wong, Maud Wurmser, Rémi Pierre, Francina Langa, Marcio Do Cruzeiro, Alain Schmitt, Jean-Paul Concordet, Athanassia Sotiropoulos, Jeffrey Dilworth, Daan Noordermeer, Frédéric Relaix, Iori Sakakibara, Pascal Maire

Topaz1, an essential gene for murine spermatogenesis, down-regulates the expression of numerous testis-specific long non-coding RNAs
Manon Chadourne, Elodie Poumerol, Luc Jouneau, Bruno Passet, Johan Castille, Eli Sellem, Eric Pailhoux, Béatrice Mandon-Pépin

The genetic architecture underlying body-size traits plasticity over different temperatures and developmental stages in Caenorhabditis elegans
Muhammad I. Maulana, Joost A.G. Riksen, Basten L. Snoek, Jan E. Kammenga, Mark G. Sterken

OCT4 interprets and enhances nucleosome flexibility
Caitlin M. MacCarthy, Jan Huertas, Claudia Ortmeier, Hermann vom Bruch, Deike Reinke, Astrid Sander, Tim Bergbrede, Hans R. Schöler, Vlad Cojocaru

Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage
Elisabetta Morini, Dadi Gao, Emily M. Logan, Monica Salani, Aram J. Krauson, Anil Chekuri, Yei-Tsung Chen, Ashok Ragavendran, Probir Chakravarty, Serkan Erdin, Alexei Stortchevoi, Jesper Q. Svejstrup, Michael E. Talkowski, Susan A. Slaugenhaupt

Drosophila fabp is a retinoid-inducible gene required for Rhodopsin-1 homeostasis and photoreceptor survival
Huai-Wei Huang, Hyung Don Ryoo

A complex CTCF binding code defines TAD boundary structure and function
Li-Hsin Chang, Sourav Ghosh, Andrea Papale, Mélanie Miranda, Vincent Piras, Jéril Degrouard, Mallory Poncelet, Nathan Lecouvreur, Sébastien Bloyer, Amélie Leforestier, David Holcman, Daan Noordermeer

TBX5 drives Aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development
Scott A. Rankin, Jeffrey D. Steimle, Xinan H. Yang, Ariel B. Rydeen, Kunal Agarwal, Praneet Chaturvedi, Kohta Ikegami, Michael J. Herriges, Ivan P. Moskowitz, Aaron M. Zorn

Genomic organization of the autonomous regulatory domain of eyeless locus in Drosophila melanogaster
Shreekant Verma, Rashmi U Pathak, Rakesh K Mishra

| Stem cells, regeneration & disease modelling

Measurement of activity of developmental signal transduction pathways to quantify stem cell pluripotency and phenotypically characterize differentiated cells
Yvonne Wesseling-Rozendaal, Laurent Holtzer, Wim Verhaegh, Anja van de Stolpe

Embryonic stem cells from Bartsch, et al.

Translational specialization in pluripotency by RBPMS poises future lineage-decisions
Deniz Bartsch, Kaustubh Kalamkar, Gaurav Ahuja, Hisham Bazzi, Argyris Papantonis, Leo Kurian

Multipotent progenitors and hematopoietic stem cells arise independently during the endothelial to hematopoietic transition in the early mouse embryo
Tessa Dignum, Barbara Varnum-Finney, Sanjay Srivatsan, Stacey Dozono, Olivia Waltner, Adam Heck, Cynthia Nourigat-McKay, Dana L. Jackson, Shahin Rafii, Cole Trapnell, Irwin D. Bernstein, Brandon Hadland

Germline Sex Determination regulates sex-specific signaling between germline stem cells and their niche
Pradeep Kumar Bhaskar, Sheryl Southard, Kelly Baxter, Mark Van Doren

Adult Stem Cells and Niche Cells segregate gradually from common precursors that build the adult Drosophila ovary during pupal development
Amy Reilein, Helen V. Kogan, Rachel Misner, Karen Sophia Park, Daniel Kalderon

Clonal inactivation of telomerase promotes accelerated stem cell differentiation
Kazuteru Hasegawa, Yang Zhao, Alina Garbuzov, M. Ryan Corces, Lu Chen, Peggie Cheung, Yuning Wei, Howard Y. Chang, Steven E. Artandi

Comparative analyses of gene expression in common marmoset and human pluripotent stem cells (PSCs) identify factors enhancing homologous recombination efficiency in the HPRT locus of human PSCs
Sho Yoshimatsu, Mayutaka Nakajima, Tsukasa Sanosaka, Tsukika Sato, Hideyuki Okano

Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells
Moyra Lawrence, Arash Shahsavari, Susanne Bornelöv, Thomas Moreau, Katarzyna Kania, Maike Paramor, Rebecca McDonald, James Baye, Marion Perrin, Maike Steindel, Paula Jimenez-Gomez, Christopher Penfold, Irina Mohorianu, Cedric Ghevaert

me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline
Lindy Jensen, Zsolt G. Venkei, George J. Watase, Bitarka Bisai, Scott Pletcher, Cheng-Yu Lee, Yukiko M. Yamashita

Cardiac Differentiation of Human Pluripotent Stem Cells Using Defined Extracellular Matrix Proteins Reveals Essential Role of Fibronectin
Jianhua Zhang, Ran Tao, Pratik A. Lalit, Juliana L. Carvalho, Yogananda Markandeya, Sean P. Palecek, Timothy J. Kamp

Surrogate production of genome edited sperm from a different subfamily by spermatogonial stem cell transplantation
Fenghua Zhang, Xianmei Li, Yongkang Hao, Yi Li, Ding Ye, Mudan He, Houpeng Wang, Zuoyan Zhu, Yonghua Sun

Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy
Mikael N.E. Sommarin, Parashar Dhapola, Fatemeh Safi, Rebecca Warfvinge, Linda Geironson Ulfsson, Eva Erlandsson, Anna Konturek-Ciesla, Ram Krishna Thakur, Charlotta Böiers, David Bryder, Göran Karlsson

Fish tails from Cacialli, et al.

Myeloid and endothelial cells cooperate to promote hematopoietic stem cells expansion in the fetal niche
Pietro Cacialli, Marie-Pierre Mailhe, Rachel Golub, Julien Y. Bertrand

A secreted proteomic footprint for stem cell pluripotency
Philip Lewis, Edina Silajzick, Helen Smith, Nicola Bates, Christopher A Smith, David Knight, Chris Denning, Daniel R Brison, Susan J Kimber

Integrity of the short arm of nuclear pore Y-complex is required for mouse embryonic stem cell growth and differentiation
Alba Gonzalez-Estevez, Annalisa Verrico, Clarisse Orniacki, Bernardo Reina-San-Martin, Valérie Doye

tiRNA signaling via stress-regulated vesicle transfer in the hematopoietic niche
Youmna S. Kfoury, Fei Ji, Michael Mazzola, David B. Sykes, Allison K. Scherer, Anthony Anselmo, Yasutoshi Akiyama, Francois Mercier, Nicolas Severe, Konstantinos D. Kokkaliaris, Thomas Brouse, Borja Saez, Jefferson Seidl, Ani Papazian, Pavel Ivanov, Michael K. Mansour, Ruslan I. Sadreyev, David T. Scadden

Isolation of the side population from adult neurogenic niches enriches for endothelial cells
Alena Kalinina, Catherine Gnyra, Yingben Xue, Diane Lagace

The Expression of Angiopoietin-1 and −2 in the Osteogenesis of Mesenchymal Stem Cells
Jinwen Chen, Guangchan Yang, Jie Guo, Yuqin Liu, Jinchen Guo, Jiatao Suo, Hongyou Yu

PLURIPOTENT STEM CELL-DERIVED CARDIOVASCULAR PROGENITORS DIFFFERENTIATED ON LAMININ 221 REGENERATE AND IMPROVE FUNCTION OF INFARCTED SWINE HEARTS
Lynn Yap, Li Yen Chong, Clarissa Tan, Swarnaseetha Adusumalli, Millie Seow, Jing Guo, Zuhua Cai, Sze Jie Loo, Eric Lim, Narayan Lath, Lei Ye, Enrico G. Petretto, Karl Tryggvason

TAZ/TEAD complex regulates TGF-β1-mediated fibrosis in iPSC-derived renal organoids
Xiaoping Yang, Marco Delsante, Parnaz Daneshpajouhnejad, Paride Fenaroli, Kira Perzel Mandell, Xiaoxin Wang, Shogo Takahashi, Marc K. Halushka, Jeffrey B. Kopp, Moshe Levi, Avi Z. Rosenberg

A comprehensive transcriptome signature of murine hematopoietic stem cell aging
Arthur Flohr Svendsen, Daozheng Yang, KyungMok Kim, Seka Lazare, Natalia Skinder, Erik Zwart, Anna Mura-Meszaros, Albertina Ausema, Björn von Eyss, Gerald de Haan, Leonid Bystrykh

Epigenomic profiling of stem cells within the pilosebaceous unit identifies PRDM16 as a regulator of sebaceous gland homeostasis
Rizwan Rehimi, Giuliano Crispatzu, Carlos Andrés Chacón-Martínez, Tore Bleckwehl, Giada Mantellato, Gökcen Gözüm, Mathieu Clément-Ziza, Sara A. Wickström, Catherin Niemann, Carien Niessen, Alvaro Rada-Iglesias

Functional, metabolic and transcriptional maturation of stem cell derived beta cells
Diego Balboa, Tom Barsby, Väinö Lithovius, Jonna Saarimäki-Vire, Muhmmad Omar-Hmeadi, Oleg Dyachok, Hossam Montaser, Per-Eric Lund, Mingyu Yang, Hazem Ibrahim, Anna Näätänen, Vikash Chandra, Helena Vihinen, Eija Jokitalo, Jouni Kvist, Jarkko Ustinov, Anni I. Nieminen, Emilia Kuuluvainen, Ville Hietakangas, Pekka Katajisto, Joey Lau, Per-Ola Carlsson, Sebastian Barg, Anders Tengholm, Timo Otonkoski

Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from human induced pluripotent stem cells
Naritaka Tamaoki, Stefan Siebert, Takuya Maeda, Ngoc-Han Ha, Meghan L. Good, Yin Huang, Suman Kumar Vodnala, Juan J. Haro-Mora, Naoya Uchida, John F. Tisdale, Colin L. Sweeney, Uimook Choi, Julie Brault, Sherry Koontz, Harry L. Malech, Yasuhiro Yamazaki, Risa Isonaka, David S. Goldstein, Masaki Kimura, Takanori Takebe, Jizhong Zou, David F. Stroncek, Pamela G. Robey, Michael J. Kruhlak, Nicholas P. Restifo, Raul Vizcardo

A Single Cell Atlas of Spared Tissue Below a Spinal Cord Injury Reveals Cellular Mechanisms of Repair
Kaya JE Matson, Daniel E Russ, Claudia Kathe, Dragan Maric, Isabelle Hua, Jonathan Krynitsky, Randall Pursley, Anupama Sathyamurthy, Jordan W Squair, Gregoire Courtine, Ariel J Levine

Aerobic glycolysis is important for zebrafish larval wound closure and tail regeneration
Claire A. Scott, Tom J. Carney, Enrique Amaya

Single-cell resolution of MET and EMT programs during zebrafish fin regeneration
Weishene Joyce Tang, Claire Watson, Theresa A Olmstead, Christopher H Allan, Ronald Y Kwon

Plagl1 is part of the mammalian retinal injury response and a critical regulator of Müller glial cell quiescence
Yacine Touahri, Luke Ajay David, Yaroslav Ilnytskyy, Edwin van Oosten, Joseph Hanna, Nobuhiko Tachibana, Lata Adnani, Jiayi Zhao, Mary Hoffman, Rajiv Dixit, Laurent Journot, Yves Sauve, Igor Kovalchuk, Isabelle Aubert, Jeffrey Biernaskie, Carol Schuurmans

Co-targeting myelin inhibitors and CSPGs markedly enhances regeneration of GDNF-stimulated, but not conditioning-lesioned, sensory axons into the spinal cord
Jinbin Zhai, Hyukmin Kim, Seung Baek Han, Meredith Manire, Rachel Yoo, Shuhuan Pang, George M. Smith, Young-Jin Son

Regeneration in the adult Drosophila brain
Kassi L. Crocker, Khailee Marischuk, Stacey A. Rimkus, Hong Zhou, Jerry C.P. Yin, Grace Boekhoff-Falk

Necrosis-induced apoptosis promotes regeneration in Drosophila wing imaginal discs
Jacob Klemm, Michael J. Stinchfield, Robin E. Harris

Heterogeneous pdgfrβ+ cells regulate coronary vessel development and revascularization during heart regeneration
Subir Kapuria, Haipeng Bai, Juancarlos Fierros, Ying Huang, Feiyang Ma, Tyler Yoshida, Antonio Aguayo, Fatma Kok, Katie M. Wiens, Joycelyn K. Yip, Megan L. McCain, Matteo Pellegrini, Mikiko Nagashima, Peter F. Hitchcock, Nathan D. Lawson, Michael MR Harrison, Ching-Ling Lien

Fish retinas from Magner, et al.

The microRNA miR-18a links proliferation and inflammation during photoreceptor regeneration in the injured zebrafish retina
Evin Magner, Pamela Sandoval-Sanchez, Peter F. Hitchcock, Scott M. Taylor

Regenerating axolotlimbs from Wells-Enright, et al.

Neurotrophic control of size regulation during axolotl limb regeneration
Kaylee M. Wells-Enright, Kristina Kelley, Mary Baumel, Warren A. Vieira, Catherine D. McCusker

Urgent Brain Vascular Regeneration Occurs via Lymphatic Transdifferentiation
Jingying Chen, Xiuhua Li, Rui Ni, Qi Chen, Qifen Yang, Jianbo He, Lingfei Luo

Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina
Si Chen, Kira L. Lathrop, Takaaki Kuwajima, Jeffrey M. Gross

Alzheimer’s disease-associated TM2D genes regulate Notch signaling and neuronal function in Drosophila
Jose L. Salazar, Sheng-An Yang, Yong Qi Lin, David Li-Kroeger, Paul C. Marcogliese, Samantha L. Deal, G. Gregory Neely, Shinya Yamamoto

AAV-delivery of diacylglycerol kinase kappa achieves long-term rescue of Fmr1-KO mouse model deficits of fragile X syndrome
Karima Habbas, Oktay Cakil, Boglarka Zambo, Ricardos Tabet, Fabrice Riet, Doulaye Dembele, Jean-Louis Mandel, Michaël Hocquemiller, Ralph Laufer, Françoise Piguet, Hervé Moine

Sequential defects in cardiac lineage commitment and maturation cause hypoplastic left heart syndrome
Markus Krane, Martina Dreßen, Gianluca Santamaria, Ilaria My, Christine M. Schneider, Tatjana Dorn, Svenja Laue, Elisa Mastantuono, Riccardo Berutti, Hilansi Rawat, Ralf Gilsbach, Pedro Schneider, Harald Lahm, Sascha Schwarz, Stefanie A. Doppler, Sharon Paige, Nazan Puluca, Sophia Doll, Irina Neb, Thomas Brade, Zhong Zhang, Claudia Abou-Ajram, Bernd Northoff, Lesca M. Holdt, Stefanie Sudhop, Makoto Sahara, Alexander Goedel, Andreas Dendorfer, Fleur V.Y. Tjong, Maria E. Rijlaarsdam, Julie Cleuziou, Nora Lang, Christian Kupatt, Connie Bezzina, Rüdiger Lange, Neil E. Bowles, Matthias Mann, Bruce Gelb, Lia Crotti, Lutz Hein, Thomas Meitinger, Sean Wu, Daniel Sinnecker, Peter J. Gruber, Karl-Ludwig Laugwitz, Alessandra Moretti

Developmental Alcohol Exposure in Drosophila: Effects on Adult Phenotypes and Gene Expression in the Brain
Sneha S. Mokashi, Vijay Shankar, Rebecca A. MacPherson, Rachel C. Hannah, Trudy F. C. Mackay, Robert R. H. Anholt

Mouse brains from Schlusche, et al.

Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice
Anna Katharina Schlusche, Sabine Ulrike Vay, Niklas Kleinenkuhnen, Steffi Sandke, Rafael Campos-Martin, Marta Florio, Wieland Huttner, Achim Tresch, Jochen Roeper, Maria Adele Rueger, Igor Jakovcevski, Malte Stockebrand, Dirk Isbrandt

fmr1 mutation interacts with sensory experience to alter the early development of behavior and sensory coding in zebrafish
Shuyu Zhu, Michael McCullough, Zac Pujic, Jordan Sibberas, Biao Sun, Bianca Bucknall, Lilach Avitan, Geoffrey J Goodhill

Using Human Induced Pluripotent Stem Cell Derived Organoids to Identify New Pathologies in Patients with PDX1 Mutations
Mansa Krishnamurthy, Daniel O Kechele, Taylor Broda, Xinghao Zhang, Jacob R Enriquez, Heather A McCauley, J Guillermo Sanchez, Joseph Palermo, Margaret Collins, Inas H Thomas, Haley C Neef, Amer Heider, Andrew Dauber, James M Wells

Neonatal neuronal WWOX gene therapy rescues Wwox null phenotypes
Srinivasarao Repudi, Irina Kustanovich, Sara Abu-Swai, Shani Stern, Rami I. Aqeilan

The role of Kabuki Syndrome genes KMT2D and KDM6A in development: Analysis in Human sequencing data and compared to mice and zebrafish
Rwik Sen, Ezra Lencer, Elizabeth A. Geiger, Kenneth Jones, Tamim H. Shaikh, Kristin Bruk Artinger

Mutations affecting the N-terminal domains of SHANK3 point to different pathomechanisms in neurodevelopmental disorders
Daniel Woike, Emily Wang, Debora Tibbe, Fatemeh Hassani Nia, Maria Kibæk, Martin J. Larsen, Christina R. Fagerberg, Igor Barsukov, Hans-Jürgen Kreienkamp

Autism risk gene POGZ promotes chromatin accessibility and expression of clustered synaptic genes
Eirene Markenscoff-Papadimitriou, Fadya Binyameen, Sean Whalen, James Price, Kenneth Lim, Rinaldo Catta-Preta, Emily Ling-Lin Pai, Xin Mu, Duan Xu, Katherine S. Pollard, Alex Nord, Matthew W. State, John L. Rubenstein

Novel zebrafish mutants reveal new roles for Apolipoprotein B during embryonic development and pathological conditions
Hanoch Templehof, Noga Moshe, Inbal Avraham-Davidi, Karina Yaniv

| Plant development

Nuclear retention of pre-mRNA involving Cajal bodies during meiotic prophase in plants
Magda Rudzka, Malwina Hyjek-Składanowska, Patrycja Wróblewska-Ankiewicz, Karolina Majewska, Marcin Gołębiewski, Marcin Sikora, Dariusz Jan Smoliński, Agnieszka Kołowerzo-Lubnau

Arabidopsis seedlings in Han, et al.

Rapid auxin-mediated phosphorylation of Myosin regulates trafficking and polarity in Arabidopsis
Huibin Han, Inge Verstraeten, Mark Roosjen, Ewa Mazur, Nikola Rýdza, Jakub Hajný, Krisztina Ötvös, Dolf Weijers, Jiří Friml

CRISPR-Cas12a genome editing at the whole-plant level using two compatible RNA virus vectors
Mireia Uranga, Marta Vazquez-Vilar, Diego Orzáez, José-Antonio Daròs

The hexose transporter SWEET5 confers galactose sensitivity to Arabidopsis pollen via the galactokinase GALK
Jiang Wang, Ya-Chi Yu, Ye Li, Li-Qing Chen

NAC transcription factor RD26 is a regulator of root hair morphogenic plasticity
Iman Kamranfar, Salma Balazadeh, Bernd Mueller-Roeber

Locally restricted glucose availability in the embryonic hypocotyl determines seed germination under ABA treatment
Xueyi Xue, Ya-Chi Yu, Yue Wu, Huiling Xue, Li-Qing Chen

The ORGAN SIZE (ORG) locus contributes to isometric gigantism in domesticated tomato
Mateus Henrique Vicente, Kyle MacLeod, Cassia Regina Fernandes Figueiredo, Antonio Vargas de Oliveira Figueira, Fady Mohareb, Zoltán Kevei, Andrew J. Thompson, Agustin Zsögön, Lázaro Eustáquio Pereira Peres

Spatiotemporal cytokinin signaling imaging reveals IPT3 function in nodule development in Medicago truncatula
Paolo M. Triozzi, Thomas B. Irving, Henry W. Schmidt, Zachary P. Keyser, Sanhita Chakraborty, Kelly M. Balmant, Wendell J. Pereira, Christopher Dervinis, Kirankumar S. Mysore, Jiangqi Wen, Jean-Michel Ané, Matias Kirst, Daniel Conde

PSK signaling controls ABA homeostasis and signaling genes and maintains shoot growth under osmotic stress
Komathy Rajamanickam, Martina D. Schönhof, Bettina Hause, Margret Sauter

Abscisic acid modulates auxin-responsive hypocotyl elongation
Ryan J. Emenecker, Joseph Cammarata, Irene Yuan, Lucia C. Strader

The F-box protein AFF1 regulates ARF protein accumulation to regulate auxin response
Hongwei Jing, David A. Korasick, Ryan J. Emenecker, Nicholas Morffy, Edward G. Wilkinson, Samantha K. Powers, Lucia C. Strader

Transcriptional condensates formed by phase-separated ALOG family proteins control shoot meristem maturation for flowering
Xiaozhen Huang, Nan Xiao, Yue Xie, Lingli Tang, Yueqin Zhang, Yuan Yu, Cao Xu

Torsions-Driven Root Helical Growth, Waving And Skewing In Arabidopsis
Ke Zhou

Cyclic Nucleotide-Gated Ion Channel 2 modulates auxin homeostasis and signaling
Sonhita Chakraborty, Masatsugu Toyota, Wolfgang Moeder, Kimberley Chin, Alex Fortuna, Marc Champigny, Steffen Vanneste, Simon Gilroy, Tom Beeckman, Eiji Nambara, Keiko Yoshioka

Maize ears from Demesa-Arevalo, et al.

Maize RAMOSA3 accumulates in nuclear condensates enriched in RNA POLYMERASE II isoforms during the establishment of axillary meristem determinacy
Edgar Demesa-Arevalo, Maria Jazmin Abraham-Juarez, Xiaosa Xu, Madelaine Bartlett, David Jackson

Class II LBD genes ZmLBD5 and ZmLBD33 regulate gibberellin and abscisic acid biosynthesis
Jing Xiong, Xuanjun Feng, Weixiao Zhang, Xianqiu Wang, Yue Hu, Xuemei Zhang, Fengkai Wu, Wei Guo, Wubing Xie, Qingjun Wang, Jie Xu, Yanli Lu

FRUITFULL-like genes regulate flowering time and inflorescence architecture in tomato
Xiaobing Jiang, Greice Lubini, José Hernandes-Lopes, Kim Rijnsburger, Vera Veltkamp, Ruud A. de Maagd, Gerco C. Angenent, Marian Bemer

SAMBA controls the rate of cell division in maize development through APC/C interaction
Pan Gong, Michiel Bontinck, Kirin Demuynck, Jolien De Block, Kris Gevaert, Dominique Eeckhout, Geert Persiau, Stijn Aesaert, Griet Coussens, Mieke Van Lijsebettens, Laurens Pauwels, Geert De Jaeger, Dirk Inzé, Hilde Nelissen

H2A ubiquitination is essential for Polycomb Repressive Complex 1-mediated gene regulation in Marchantia polymorpha
Shujing Liu, Minerva S. Trejo-Arellano, Yichun Qiu, D. Magnus Eklund, Claudia Köhler, Lars Hennig

Sugar Signaling Induces Dynamic Changes during Meristem Development in Arabidopsis
Magdalena Musialak-Lange, Katharina Fiddeke, Annika Franke, Friedrich Kragler, Christin Abel, Vanessa Wahl

A heterochromatic knob reducing the flowering time in maize
Renata Flávia Carvalho, Margarida Lopes Rodrigues Aguiar-Perecin, Wellington Ronildo Clarindo, Roberto Fristche-Neto, Mateus Mondin

The barley mutant multiflorus2.b reveals quantitative genetic variation for new spikelet architecture
Ravi Koppolu, Guojing Jiang, Sara G Milner, Quddoos H Muqaddasi, Twan Rutten, Axel Himmelbach, Nils Stein, Martin Mascher, Thorsten Schnurbusch

A CENH3 mutation promotes meiotic exit and restores fertility in SMG7-deficient Arabidopsis
Claudio Capitao, Sorin Tanasa, Jaroslav Fulnecek, Vivek K. Raxwal, Svetlana Akimcheva, Petra Bulankova, Pavlina Mikulkova, Inna Lermontova, Ortrun Mittelsten Scheid, Karel Riha

Root meristem shaping via brassinosteroid-controlled cell geometry
Y. Fridman, S. Strauss, G. Horev, M. Ackerman-Lavert, A Reiner Benaim, B Lane, R.S. Smith, S. Savaldi-Goldstein

Altered metal distribution in the sr45-1 Arabidopsis mutant causes developmental defects
Steven Fanara, Marie Schloesser, Marc Hanikenne, Patrick Motte

Tomato hypocotyls from Larriba, et al.

Tissue-specific metabolic reprogramming during wound induced de novo organ formation in tomato hypocotyl explants
Eduardo Larriba, Ana Belen Sanchez-Garcia, Cristina Martinez-Andujar, Alfonso Albacete, Jose Manuel Perez-Perez Sr.

Jasmonate inhibits adventitious root initiation through transcriptional repression of CKX1 and activation of RAP2.6L transcription factor in Arabidopsis
Asma Dob, Abdellah Lakehal, Ondrej Novak, Catherine Bellini

Generation of guard cell RNA-seq transcriptomes during progressive drought and recovery using an adapted INTACT protocol for Arabidopsis thaliana shoot tissue
Anna van Weringh, Asher Pasha, Eddi Esteban, Paul J. Gamueda, Nicholas J. Provart

Transcriptomic analysis of temporal shifts in berry development between two grapevine cultivars of the Pinot family reveals potential ripening-regulative genes
Jens Theine, Daniela Holtgräwe, Katja Herzog, Florian Schwander, Anna Kicherer, Ludger Hausmann, Prisca Viehöver, Reinhard Töpfer, Bernd Weisshaar

DNA methylation affects pre-mRNA transcriptional initiation and processing in Arabidopsis
Qiuhui Li, Shengjie Chen, Amy Wing-Sze Leung, Yaqin Liu, Yan Xin, Li Zhang, Hon-Ming Lam, Ruibang Luo, Shoudong Zhang

Light-triggered and phosphorylation-dependent 14-3-3 association with NONPHOTOTROPIC HYPOCOTYL 3 is required for hypocotyl phototropism
Lea Reuter, Tanja Schmidt, Prabha Manishankar, Christian Throm, Jutta Keicher, Andrea Bock, Claudia Oecking

Arabidopsis roots from Graeff & Hardtke

Metaphloem development in the Arabidopsis root tip
Moritz Graeff, Christian S. Hardtke

Integration of embryo-endosperm interaction into a holistic and dynamic picture of seed development using a rice mutant with notched-belly grains
Yang Tao, Lu An, Feng Xiao, Ganghua Li, Yanfeng Ding, Matthew J. Paul, Zhenghui Liu

Cell layer-specific expression of the B-class MADS-box gene PhDEF drives petal tube or limb development in petunia flowers
M. Chopy, Q. Cavallini-Speisser, P. Chambrier, P. Morel, J. Just, V. Hugouvieux, S. Rodrigues Bento, C. Zubieta, M. Vandenbussche, M. Monniaux

Repression of CHROMOMETHYLASE 3 Prevents Epigenetic Collateral Damage in Arabidopsis
Ranjith K. Papareddy, Katalin Páldi, Anna D. Smolka, Patrick Hüther, Claude Becker, Michael D. Nodine

Integration of computational modeling and quantitative cell physiology reveals central parameters for the brassinosteroid-regulated elongation growth along the axis of the Arabidopsis root tip
Ruth Großeholz, Friederike Wanke, Nina Glöckner, Leander Rohr, Stefan Scholl, Karin Schumacher, Ursula Kummer, Klaus Harter

The Boundary-Expressed EPIDERMAL PATTERNING FACTOR-LIKE2 Gene Encoding a Signaling Peptide Promotes Cotyledon Growth during Arabidopsis thaliana Embryogenesis
Rina Fujihara, Naoyuki Uchida, Toshiaki Tameshige, Nozomi Kawamoto, Yugo Hotokezaka, Takumi Higaki, Ruediger Simon, Keiko U Torii, Masao Tasaka, Mitsuhiro Aida

O-glycosylation regulates plant developmental transitions downstream of miR156
Krishna Vasant Mutanwad, Alexandra Baekelandt, Nicole Neumayer, Claudia Freitag, Isabella Zangl, Dirk Inzé, Doris Lucyshyn

A cis-regulatory atlas in maize at single-cell resolution
Alexandre P. Marand, Zongliang Chen, Andrea Gallavotti, Robert J. Schmitz

| Evo-devo

Axis formation in annual killifish: Nodal coordinates morphogenesis in absence of Huluwa prepatterning
Philip B. Abitua, Deniz C. Aksel, Alexander F. Schier

Insm1-expressing neurons and secretory cells develop from a common pool of progenitors in the sea anemone Nematostella vectensis
Océane Tournière, Henriette Busengdal, James M. Gahan, Fabian Rentzsch

The neuroblast timer gene nubbin exhibits functional redundancy with gap genes to regulate segment identity in Tribolium
Olivia RA Tidswell, Matthew A Benton, Michael E Akam

Eye morphogenesis in the blind Mexican cavefish
Lucie Devos, François Agnès, Joanne Edouard, Victor Simon, Laurent Legendre, Naima El Khallouki, Sosthène Barbachou, Frédéric Sohm, Sylvie Rétaux

Squid eyes from Neal, et al.

Co-option of the Limb Patterning Program in Cephalopod Lens Development
Stephanie Neal, Kyle J. McCulloch, Francesca Napoli, Christina M. Daly, James H. Coleman, Kristen M. Koenig

Molluscan dorsal-ventral patterning relying on bmp2/4 and chordin provides insights into spiralian development and bilaterian evolution
Sujian Tan, Pin Huan, Baozhong Liu

Evolution of a cytoplasmic determinant: evidence for the biochemical basis of functional evolution of a novel germ line regulator
Leo Blondel, Savandara Besse, Cassandra G. Extavour

Evolutionary dynamics of sex-biased genes expressed in cricket brains and gonads
Carrie A. Whittle, Arpita Kulkarni, Cassandra G. Extavour

Segment number threshold determines juvenile onset of germline cluster proliferation in Platynereis dumerilii
Emily Kuehn, David S. Clausen, Ryan W. Null, Bria M. Metzger, Amy D. Willis, B. Duygu Özpolat

Fly phalluses from Rice, et al.

Resolving Between Novelty and Homology in the Rapidly Evolving Phallus of Drosophila
Gavin R. Rice, Jean R. David, Nicolas Gompel, Amir Yassin, Mark Rebeiz

Activation of EGFR signaling by Tc-Vein and Tc-Spitz regulates the metamorphic transition in the red flour beetle Tribolium castaneum
Sílvia Chafino, David Martín, Xavier Franch-Marro

The unique neuronal structure and neuropeptide repertoire in the ctenophore Mnemiopsis leidyi shed light on the evolution of animal nervous systems
Maria Y Sachkova, Eva-Lena Nordmann, Joan J Soto-Àngel, Yasmin Meeda, Bartłomiej Górski, Benjamin Naumann, Daniel Dondorp, Marios Chatzigeorgiou, Maike Kittelmann, Pawel Burkhardt

Developmental series of gene expression clarifies maternal mRNA provisioning and maternal-to-zygotic transition in the reef-building coral Montipora capitata
E Chille, E Strand, M Neder, V Schmidt, M Sherman, T Mass, HM Putnam

Tempo and mode of gene expression evolution in the brain across Primates
Amy L. Bauernfeind, Trisha M. Zintel, Jason Pizzollo, John J. Ely, Mary Ann Raghanti, William D. Hopkins, Patrick R. Hof, Chet C. Sherwood, Courtney C. Babbitt

A muscle-related contractile tissue specified by MRTF-activity in Porifera
J. Colgren, S.A. Nichols

Novel neuroanatomical integration and scaling define avian brain shape evolution and development
Akinobu Watanabe, Amy M. Balanoff, Paul M. Gignac, M. Eugenia Gold, Mark A. Norell

Rapid mosaic brain evolution under artificial selection for relative telencephalon size in the guppy (Poecilia reticulata)
Stephanie Fong, Björn Rogell, Mirjam Amcoff, Alexander Kotrschal, Wouter van der Bijl, Séverine D. Buechel, Niclas Kolm

Sexual Reproduction in Bdelloid Rotifers
Veronika N. Laine, Timothy Sackton, Matthew Meselson

Evolution of multicellularity and unicellularity in yeast S. cerevisiae to study reversibility of evolutionary trajectories
Phaniendra Alugoju, Anjali Mahilkar, Supreet Saini

Human-derived alleles in SOST and RUNX2 3′UTRs cause differential regulation in a bone cell-line model
Juan Moriano, Núria Martínez-Gil, Alejandro Andirkó, Susana Balcells, Daniel Grinberg, Cedric Boeckx

Functional characterization of a “plant-like” HYL1 homolog in the cnidarian Nematostella vectensis indicates a conserved involvement in microRNA biogenesis
Abhinandan Mani Tripathi, Arie Fridrich, Magda Lewandowska, Yehu Moran

Lower promoter activity of the ST8SIA2 gene has been favored in evolving human collective brains
Toshiyuki Hayakawa, Masahiro Terahara, Naoko T. Fujito, Takumi Matsunaga, Kosuke Teshima, Masaya Hane, Ken Kitajima, Chihiro Sato, Naoyuki Takahata, Yoko Satta

Widespread retention of ohnologs in key developmental gene families following whole genome duplication in arachnopulmonates
Amber Harper, Luis Baudouin Gonzalez, Anna Schönauer, Ralf Janssen, Michael Seiter, Michaela Holzem, Saad Arif, Alistair P. McGregor, Lauren Sumner-Rooney

Development of larvae of the Australian blowfly, Calliphora augur (Diptera: Calliphoridae), at constant temperatures
Donnah M. Day, Nathan J. Butterworth, Anirudh Tagat, Gregory Markowsky, James F. Wallman

Phylotranscriptomics points to multiple independent origins of multicellularity and cellular differentiation in the volvocine algae
Charles Ross Lindsey, Frank Rosenzweig, Matthew D Herron

Why is the expression of so many genes rhythmic? Energetic cost explains protein rhythmicity and expression noise control explains mRNA rhythmicity
David Laloum, Marc Robinson-Rechavi

The hourglass model of evolutionary conservation during embryogenesis extends to developmental enhancers with signatures of positive selection
Jialin Liu, Rebecca R. Viales, Pierre Khoueiry, James P. Reddington, Charles Girardot, Eileen E. M. Furlong, Marc Robinson-Rechavi

Cell Biology

Glycogen-dependent demixing of frog egg cytoplasm at increased crowding
James F. Pelletier, Christine M. Field, Margaret Coughlin, Lillia Ryazanova, Matthew Sonnett, Martin Wühr, Timothy J. Mitchison

Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons
Ines Hahn, Andre Voelzmann, Jill Parkin, Judith Fuelle, Paula G Slater, Laura A Lowery, Natalia Sanchez-Soriano, Andreas Prokop

In vitro condensates from Bose, et al.

Liquid-to-solid phase transition of oskar RNP granules is essential for their function in the Drosophila germline
Mainak Bose, Julia Mahamid, Anne Ephrussi

Actin polymerization and crosslinking drive left-right asymmetry in single cell and cell collectives
Y. H. Tee, W. J. Goh, X. Yong, H. T. Ong, J. Hu, I. Y. Y. Tay, S. Shi, S. Jalal, S. F. H. Barnett, P. Kanchanawong, W. Huang, J. Yan, V. Thiagarajan, A. D. Bershadsky

Enhanced RhoA signaling stabilizes E-cadherin in migrating epithelial monolayers
Shafali Gupta, Kinga Duszyc, Suzie Verma, Srikanth Budnar, Xuan Liang, Guillermo A. Gomez, Philippe Marcq, Ivar Noordstra, Alpha S. Yap

Nuclei are mobile processors enabling specialization in a gigantic single-celled syncytium
Tobias Gerber, Cristina Loureiro, Nico Schramma, Siyu Chen, Akanksha Jain, Anne Weber, Anne Weigert, Malgorzata Santel, Karen Alim, Barbara Treutlein, J. Gray Camp

Alternative splicing of pericentrin contributes to cell cycle control in cardiomyocytes
Jakob Steinfeldt, Robert Becker, Silvia Vergarajauregui, Felix B. Engel

The Hippo pathway regulates density-dependent proliferation of iPSC-derived cardiac myocytes
Abigail C. Neininger, Xiaozhaun Dai, Qi Liu, Dylan T. Burnette

Phosphoproteomics of ATR Signaling in Prophase I of Mouse Meiosis
Jennie R. Sims, Vitor M. Faça, Catalina Pereira, Gerardo A. Arroyo-Martinez, Raimundo Freire, Paula E. Cohen, Robert S. Weiss, Marcus B. Smolka

Egalitarian feeds forward to Staufen to inhibit Dynein during mRNP transport
Imre Gáspár, Ly Jane Phea, Anne Ephrussi

Cytoskeletal vimentin regulates cell size and autophagy through mTORC1 signaling
Ponnuswamy Mohanasundaram, Leila S Coelho Rato, Mayank Modi, Marta Urbanska, Franziska Lautenschläger, Fang Cheng, John E Eriksson

Dividing cells in Chann, et al.

A Scribble-E-cadherin complex controls daughter cell patterning by multiple mechanisms
Anchi S. Chann, Ye Chen, Tanja Kinwel, Patrick O. Humbert, Sarah M. Russell

A gene duplication of a septin provides a developmentally-regulated filament length control mechanism
Kevin S. Cannon, Jose M. Vargas-Muniz, Neil Billington, Ian Seim, Joanne Ekena, James Sellers, Peter Philippsen, Amy. S. Gladfelter

Cytoplasmic pressure maintains epithelial integrity and inhibits cell motility
Pragati Chengappa, Tia M. Jones, James M. Cowan, Devneet Kainth, Ryan J. Petrie

Temporal resolution of melanogenesis determine fatty acid metabolism as key skin pigment regulator
Farina Sultan, Reelina Basu, Divya Murthy, Manisha Kochar, Kuldeep S. Attri, Ayush Aggrawal, Pooja Kumari, Pooja Dnyane, Archana Singh, Chetan Gadgil, Neel S. Bhavesh, Pankaj K. Singh, Vivek T. Natarajan, Rajesh S. Gokhale

Endothelial metastasis-associated protein 1 (MTA1) is an essential molecule for angiogenesis
Mizuho Ishikawa, Mitsuhiko Osaki, Narumi Uno, Takahito Ohira, Hiroyuki Kugoh, Futoshi Okada

Rho and F-actin self-organize within an artificial cell cortex
Jennifer Landino, Marcin Leda, Ani Michaud, Zachary T. Swider, Mariah Prom, Christine M. Field, William M. Bement, Anthony G. Vecchiarelli, Andrew B. Goryachev, Ann L. Miller

aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete β-arrestin-2 mediated SphK1-S1PR1-Akt signaling axis
Olivia Molinar-Inglis, Cierra A. Birch, Dequina Nicholas, Metztli Cisneros-Aguirre, Anand Patwardhan, Buxin Chen, Neil J. Grimsey, Patrick K. Gomez Menzies, Huilan Lin, Luisa J. Coronel, Mark A. Lawson, Hemal. H. Patel, JoAnn Trejo

Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis
Catalina Pereira, Gerardo A. Arroyo-Martinez, Matthew Z. Guo, Michael S. Downey, Emma R. Kelly, Kathryn J. Grive, Shantha K. Mahadevaiah, Jennie Sims, Vitor Marcel Faça, Charlton Tsai, Carl J. Schiltz, Niek Wit, Heinz Jacobs, Nathan L. Clark, Raimundo Freire, James M. A. Turner, Amy M. Lyndaker, Miguel A. Brieño-Enríquez, Paula E. Cohen, Marcus B. Smolka, Robert S. Weiss

Rab40/Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration and invasion
Erik S Linklater, Emily D Duncan, Ke-Jun Han, Algirdas Kaupinis, Mindaugas Valius, Traci R Lyons, Rytis Prekeris

Modelling

Cellular tango: How extracellular matrix adhesion choreographs Rac-Rho signaling and cell movement
Elisabeth G. Rens, Leah Edelstein-Keshet

Modelling morphogens in Song and Hyeon.

Cost-precision trade-off relation determines the optimal morphogen gradient for accurate biological pattern formation
Yonghyun Song, Changbong Hyeon

Improving the understanding of cytoneme-mediated morphogen gradients by in silico modeling
Adrián Aguirre-Tamaral, Isabel Guerrero

Effect of cellular rearrangement time delays on the rheology of vertex models for confluent tissues
Gonca Erdemci-Tandogan, M. Lisa Manning

Multiple morphogens and rapid elongation promote segmental patterning during development
Yuchi Qiu, Lianna Fung, Thomas F. Schilling, Qing Nie

The need for high-quality oocyte mitochondria at extreme ploidy dictates germline development
Marco Colnaghi, Andrew Pomiankowski, Nick Lane

HYBRID REACTION-DIFFUSION AND CLOCK-AND-WAVEFRONT MODEL FOR THE ARREST OF OSCILLATIONS IN THE SOMITOGENESIS SEGMENTATION CLOCK
Jesús Pantoja-Hernández, Víctor F. Breña-Medina, Moisés Santillán

Oscillations and Bifurcation Structure of Reaction-Diffusion Model for Cell Polarity Formation
Masataka Kuwamura, Hirofumi Izuhara, Shin-ichiro Ei

Polarized interfacial tension induces collective migration of cells, as a cluster, in a three-dimensional tissue
Satoru Okuda, Katsuhiko Sato

Reviews

Tissue hydraulics: physics of lumen formation and interaction
Alejandro Torres-Sánchez, Max Kerr Winter, Guillaume Salbreux

Tools & Resources

Optogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis
Kei Yamamoto, Haruko Miura, Motohiko Ishida, Satoshi Sawai, Yohei Kondo, Kazuhiro Aoki

High-Resolution, Large Imaging Volume, and Multi-View Single Objective Light-Sheet Microscopy
Bin Yang, Merlin Lange, Alfred Millett-Sikking, Ahmet Can Solak, Shruthi Vijay Kumar, Wanpeng Wang, Hirofumi Kobayashi, Matthew N. McCarroll, Lachlan W. Whitehead, Reto P. Fiolka, Thomas B. Kornberg, Andrew G. York, Loic A. Royer

ZAF — An Open Source Fully Automated Feeder for Aquatic Facilities
Merlin Lange, Ahmet Can Solak, Shruthi VijayKumar, Hirofumi Kobayashi, Bin Yang, Loic Alain Royer

Capturing Membrane Trafficking Events During 3D Angiogenic Development in Vitro
Caitlin R. Francis, Erich J. Kushner

3D pancreas from Glorieux, et al.

Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions
Laura Glorieux, Aleksandra Sapala, David Willnow, Manon Moulis, Shlomit Edri, Jean-Francois Darrigrand, Anat Schonblum, Lina Sakhneny, Laura Schaumann, Harold F Gomez, Christine Lang, Lisa Conrad, Fabien Guillemot, Shulamit Levenberg, Limor Landsman, Dagmar Iber, Christophe Pierreux, Francesca M Spagnoli

A Cre-dependent CRISPR/dCas9 system for gene expression regulation in neurons
Nancy V. N. Carullo, Jenna E. Hinds, Jasmin S. Revanna, Jennifer J. Tuscher, Allison J. Bauman, Jeremy J. Day

Computational anatomy and geometric shape analysis enables analysis of complex craniofacial phenotypes in zebrafish
Kelly M. Diamond, Sara M. Rolfe, Ronald Y. Kwon, A. Murat Maga

Multiview tiling light sheet microscopy for 3D high resolution live imaging
Mostafa Aakhte, H.-Arno J. Müller

Single-Molecule Tracking of Chromatin-Associated Proteins in the C. elegans Gonad
Lexy von Diezmann, Ofer Rog

Microfluidic-based imaging of complete C. elegans larval development
Simon Berger, Silvan Spiri, Andrew deMello, Alex Hajnal

CRISPR Knock-in Designer: automatic oligonucleotide design software to introduce point mutations using CRISPR/Cas9
Sergey V. Prykhozhij, Vinothkumar Rajan, Kevin Ban, Jason N. Berman

Measuring nonapoptotic caspase activity with a transgenic reporter in mice
P. J. Nicholls, Thomas F. Pack, Nikhil M. Urs, Sunil Kumar, Yang Zhou, Gabor Turu, Evan Calabrese, Wendy L. Roberts, Ping Fan, Valeriy G. Ostapchenko, Monica S. Guzman, Flavio Beraldo, Vania F. Prado, Marco A. M. Prado, Ivan Spasojevic, Joshua C. Snyder, Kafui Dzirasa, G. Allan Johnson, Marc G. Caron

Multiphoton imaging of neural structure and activity in Drosophila through the intact cuticle
Max Jameson Aragon, Mengran Wang, Aaron T. Mok, Jamien Shea, Haein Kim, Nathan Barkdull, Chris Xu, Nilay Yapici

Protein visualization and manipulation in Drosophila through the use of epitope tags recognized by nanobodies
Jun Xu, Ah-Ram Kim, Ross W. Cheloha, Fabian A. Fischer, Joshua Shing Shun Li, Yuan Feng, Emily Stoneburner, Richard Binari, Stephanie E. Mohr, Jonathan Zirin, Hidde Ploegh, Norbert Perrimon

Technical advances in the development of zonation liver in vitro systems that incorporate localized Wnt activating signals
Eider Valle-Encinas, Michael Dawes, Carmen Velasco Martinez, Kate McSweeney, Miryam Müller, Tom Bird, Trevor Dale

Photoswitchable epothilone-based microtubule stabilisers allow GFP-imaging-compatible, optical control over the microtubule cytoskeleton
Li Gao, Joyce C. M. Meiring, Constanze Heise, Ankit Rai, Adrian Müller-Deku, Anna Akhmanova, Julia Thorn-Seshold, Oliver Thorn-Seshold

Zebrafish heads from Davis, et al.

Rapid generation of pigment free, immobile zebrafish embryos and larvae in any genetic background using CRISPR-Cas9 dgRNPs
Andrew E. Davis, Daniel Castranova, Brant M. Weinstein

A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes
Tanya Grancharova, Kaytlyn A. Gerbin, Alexander B. Rosenberg, Charles M. Roco, Joy Arakaki, Colette DeLizzo, Stephanie Q. Dinh, Rory Donovan-Maiye, Matthew Hirano, Angelique Nelson, Joyce Tang, Julie A. Theriot, Calysta Yan, Vilas Menon, Sean P. Palecek, Georg Seelig, Ruwanthi N. Gunawardane

Oligopaint DNA FISH as a tool for investigating meiotic chromosome dynamics in the silkworm, Bombyx mori
Leah F. Rosin, Jose Gil Jr., Ines A. Drinnenberg, Elissa P. Lei

A Focal Adhesion Filament Cross-correlation Kit for fast, automated segmentation and correlation of focal adhesions and actin stress fibers in cells
Lara Hauke, Shwetha Narasimhan, Andreas Primeßnig, Irina Kaverina, Florian Rehfeldt

tdLanYFP, a yellow, bright, photostable and pH insensitive fluorescent protein for live cell imaging and FRET-based sensing strategies
Y. Bousmah, H. Valenta, G. Bertolin, U. Singh, V. Nicolas, H. Pasquier, M. Tramier, F. Merola, M. Erard

A new method for obtaining bankable and expandable adult-like microglial cells
Min-Jung You, Chan Rim, Youn-Jung Kang, Min-Soo Kwon

Standardized quality control workflow to evaluate the reproducibility and differentiation potential of human iPSCs into neurons
Carol X.-Q. Chen, Narges Abdian, Gilles Maussion, Rhalena A. Thomas, Iveta Demirova, Eddie Cai, Mahdieh Tabatabaei, Lenore K. Beitel, Jason Karamchandani, Edward A. Fon, Thomas M. Durcan

Marker-assisted mapping enables effective forward genetic analysis in the arboviral vector Aedes aegypti, a species with vast recombination deserts
Chujia Chen, Austin Compton, Katerina Nikolouli, Aihua Wang, Azadeh Aryan, Atashi Sharma, Yumin Qi, Camden Delinger, Melanie Hempel, Antonios Augustinos, David W. Severson, Kostas Bourtzis, Zhijian Tu

Single-shot phase contrast microscopy using polarisation-resolved differential phase contrast
R. Kalita, W. Flanagan, J. Lightley, S. Kumar, Y. Alexandrov, E. Garcia, M. Hintze, M Barkoulas, C. Dunsby, P.M.W. French

A Dual-Color Tyr-FISH Method for Visualizing Genes/Markers on Plant Chromosomes to Create Integrated Genetic and Cytogenetic Maps
Natalya Kudryavtseva, Aleksey Ermolaev , Gennady Karlov , Ilya Kirov , Masayoshi Shigyo, Shusei Sato , Ludmila Khrustaleva

An ELISA-based method for rapid genetic screens in Drosophila
Taylor R Jay, Yunsik Kang, Amanda Jefferson, Marc R Freeman

Evidence provided by high-impact cell culture studies does not support authors’ claims
Ali Burak Özkaya, Caner Geyik

Multi-color fluorescence fluctuation spectroscopy in living cells via spectral detection
Valentin Dunsing, Annett Petrich, Salvatore Chiantia

Research practice & education

A field guide to cultivating computational biology
Anne E Carpenter, Casey S Greene, Piero Carnici, Benilton S Carvalho, Michiel de Hoon, Stacey Finley, Kim-Anh Le Cao, Jerry SH Lee, Luigi Marchionni, Suzanne Sindi, Fabian J Theis, Gregory P Way, Jean YH Yang, Elana J Fertig

A tool for assessing alignment of biomedical data repositories with open, FAIR, citation and trustworthy principles
Fiona Murphy, Michael Bar-Sinai, Maryann E. Martone

How faculty define quality, prestige, and impact in research
Esteban Morales, Erin McKiernan, Meredith T. Niles, Lesley Schimanski, Juan Pablo Alperin

Preprints in motion: tracking changes between posting and journal publication
Jessica K Polka, Gautam Dey, Máté Pálfy, Federico Nanni, Liam Brierley, Nicholas Fraser, Jonathon Alexis Coates

Using Stakeholder Insights to Enhance Engagement in PhD Professional Development
Deepti Ramadoss, Amanda F. Bolgioni, Rebekah L. Layton, Janet L. Alder, Natalie Lundsteen, C. Abigail Stayart, Jodi B. Yellin, Conrad L. Smart, Susi S. Varvayanis

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New strings for the puppeteer of evolution

Posted by , on 30 April 2021

Sarah Jacquelyn Smith, Lance Davidson and Mark Rebeiz

One of the biggest mysteries in the developmental evolution field is the puzzle of how new morphological structures come about. If you think about it, every anatomical structure in the multicellular world was new at some point in time. And yet, we currently only have a rough picture of how insect wings, beetle horns, or turtle shells initially evolved. There are multiple ways that this question can be answered, and it is an exciting time to be studying how genetic programs of gene expression translate into the physical manifestations of development that form new tissue configurations. In studying one such novelty in Drosophila, we recently learned that there is more than meets the eye to generating extreme deformations in cellular shape1. We also learned to listen more carefully to our collaborators…

Novelty in Drosophila genital traits

Reproductive structures are notorious for their rapid evolution among internally fertilizing species2. The chitinous cuticle shapes in the genitalia of Drosophila melanogaster are indeed quite different from its nearest relatives. In fact, these differences in genital morphology are used to discriminate this model organism from its closest relatives3. Namely, the posterior lobe is a recently evolved hook-shaped structure which is attached to a cuticular plate known as the lateral plate (Fig. 1). The posterior lobe is highly divergent in size and shape in species that possess this structure and is absent in more distantly related Drosophila species (Fig. 1), which offer a useful reference for understanding how the genitalia likely developed before the evolution of this structure. Because the posterior lobe is present in the highly tractable Drosophila melanogaster, we can exploit the bountiful genetic tools of this model organism to examine and dissect its development. Our previous work had suggested that many genes expressed in the posterior lobe were re-deployed, or ‘co-opted’ from another organ system, the posterior spiracle4, which is an extension of the larval tracheal system. Identifying genes expressed in a structure however doesn’t tell you much about how it is built, and thus studies of genetic control mechanisms must be complemented by studies at the cellular level (and vice versa)5.

Posterior Lobe Phylogeny
Figure 1. The posterior lobe is a highly divergent structure unique to the D melanogaster clade. The lobe is the protrusion on the right-hand side (arrow), which is attached to the structure known as lateral plate which is also shown. D. ananassae and D. biarmipes are two species which express the ancestral state of lacking this structure. Scale bar = 100µM (bottom right)

The major discriminating feature of Drosophila melanogaster is a single cell tall!

When first examining the morphogenesis of the posterior lobe, we had no idea where to start. We sought the advice of a colleague across campus, Lance Davidson, who studies the biomechanics of development at the University of Pittsburgh Swanson School of Engineering. Lance was very excited to see our preliminary movies of posterior lobe development in which we monitored apical cell junctions (Movie 1). Even with this new perspective on lobe development, we had no idea exactly what was going on – we could see the apical surfaces of cells changing size and shape as the posterior lobe forms, but of course seeing these changes and knowing what processes cause these alterations are two very different things.

Movie 1. Movie of posterior lobe morphogenesis. Apical junctions are labeled by GFP-tagged armadillo protein.

However, apical cell shape changes cover only 2D of the 3D story and examining the entire shape of the cell using single cell fluorescent labeling (Movie 2), indicated that cells of the posterior lobe drastically change their shape along the apical-basal axis, and become extremely tall and thin throughout development, allowing the posterior lobe to project off of the lateral plate. Understanding how this extreme cell shape is controlled and spatially patterned would provide a context in which to connect the activity of gene regulatory networks to the patterning of cellular traits. Initially, we became quite interested in the role that cytoskeletal regulators might play in this process: patterning and stabilizing filaments of both actin and microtubules. However, our investigation uncovered an unexpected perspective on this cellular behavior.

Movie 2. Single cell labeling of the posterior lobe reveals that it is a singe cell tall. Clonal expression of mTFP1 was induced via the heat shock promoter and associated temperature shift.

Listen to your collaborators!

One day over our frequent lunchtime conversations, Lance raised the point that the posterior lobe has a cantilevered structure: it leans to one side, and he mentioned that such configuration is rare in epithelial structures. This led him to speculate that maybe we should be looking for some kind of “tether” that would pull the tissue into this arrangement. I remember quite vividly discussing this interesting model with members of the lab, and quickly dismissing it because we had never seen such a tether with our own eyes. Of course, we had only been looking at epithelial and nuclear markers at that point, and so any material that could serve as a tether might go unnoticed if it is translucent and doesn’t express the markers we used. This idea lingered in the back of our minds with little notice before we realized that perhaps Lance was onto something. Performing certain antibody stains, in particular for a septate junction protein Macroglobulin (a kind gift from Dr. Rob Ward, U. Kansas), we noticed that there was a mysterious pattern of background staining in our samples when visualized on the confocal (Figure 2). This caused us to consider the potential role of the apical extracellular matrix in building a posterior lobe.

Non-specific staining
Figure. 2. Non-specific staining of extracellular material in a stain for septate junctions (green, Macroglobulin). A cross-section of the posterior lobe (dashed lines) leans towards the detected extracellular material.

Looking beyond what the eye can see

Although basal extracellular matrices are well known to play critical roles in epithelial sheets6, recent work has shown that apical matrices are also important. Several recent papers had shown that the zona pellucida domain-encoding protein Dumpy is important for shaping the wing by attaching its distal tip to an overlying cuticle7,8. We examined a fluorescently tagged fusion protein for Dumpy, and this revealed a surprisingly intricate web of apical matrix throughout the genitalia that showed prominent connections to the posterior lobe (Movie 3). We developed fluorescent lectin staining protocols to show that this matrix exists in species that lack lobes. However, we found that strong aECM connections to where the lobe would otherwise form are much less pronounced in non-lobed species. Finally, what made this narrative compelling from an evolutionary sense is that RNAi experiments showed that Dumpy expression is required for cells of the lobe to achieve their height. Together, these results demonstrated how making prominent aECM connections is important to the formation of a new structure, and was likely subject to evolutionary changes which alter how the epithelium deposits and interacts with the matrix.

Movie 3. A GFP-tagged Dumpy expression during posterior lobe development reveals a complex and dynamic network of apical ECM.

Evolution of novelties: more than meets the eye

What makes this finding surprising is that it reveals the layers of complexity even in such a simple morphological novelty. We had not anticipated that such a complex matrix would exist outside the cells that form a morphologically novel structure. As we generally don’t look to matrices when studying cellular processes, it may be that other epithelial structures have equally elaborate and uncharted apical matrices. More broadly, the story highlights how studying novelties can unveil processes previously unknown and shows how we can zero in on proximal cellular mechanisms that assemble the elaborate structures we see in the multicellular world. Comparing cellular behaviors between species thus offers a unique window into how genetic programs drive physical processes in developing tissues. We suspect that studying the regulatory sequences and networks controlling the expression patterns of Dumpy and other apical ECM components will allow us to go beyond simplistic models of network co-option and the evolution of novelty.

References

  1. Smith, S. J., Davidson, L. A. & Rebeiz, M. Evolutionary expansion of apical extracellular matrix is required for the elongation of cells in a novel structure. Elife 9, (2020).
  2. Eberhard, W. G. Sexual selection and animal genitalia. (Harvard University Press, 1985).
  3. David, J. R., Lemeunier, F., Tsacas, L. & Yassin, A. The Historical Discovery of the Nine Species in the Drosophila melanogaster Species Subgroup. Genetics 177, 1969–1973 (2007).
  4. Glassford, W. J. et al. Co-option of an Ancestral Hox-Regulated Network Underlies a Recently Evolved Morphological Novelty. Dev. Cell 34, 520–531 (2015).
  5. Smith, S. J., Rebeiz, M. & Davidson, L. From pattern to process: studies at the interface of gene regulatory networks, morphogenesis, and evolution. Curr. Opin. Genet. Dev. 51, 103–110 (2018).
  6. Brown, N. H. Extracellular Matrix in Development: Insights from Mechanisms Conserved between Invertebrates and Vertebrates. Cold Spring Harb. Perspect. Biol. 3, a005082–a005082 (2011).
  7. Ray, R. P. et al. Patterned Anchorage to the Apical Extracellular Matrix Defines Tissue Shape in the Developing Appendages of Drosophila. Dev. Cell 34, 310–322 (2015).
  8. Etournay, R. et al. Interplay of cell dynamics and epithelial tension during morphogenesis of the Drosophila pupal wing. Elife 4, e07090 (2015).
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SciArt Profiles: Marzia Munafò

Posted by , on 30 April 2021

Our eighth profile in the series features Marzia Munafò, a postdoctoral researcher currently based in Rome.

Where are you originally from and what do you work on now?

I am originally from Rome. I recently completed my PhD in Medical Sciences at the University of Cambridge UK and I am now a postdoctoral fellow at EMBL Rome. I am a molecular biologist by training and I have worked mostly on RNA biology. During my PhD I investigated how small RNAs protect the genome from transposon activity, using Drosophila as a model organism. For my postdoc I am now focusing on understanding epigenetic inheritance and transposon regulation in mammals.

Where you always going to be a scientist?

I would say that curiosity in general has always played an important role in my life. I was an inquisitive, curious child who really enjoyed learning about the world. What initially sparked my interest for biology was learning about Mendel’s laws of inheritance in secondary school but I didn’t really consider becoming a scientist until much later. It was towards the end of high school when I realised that the one job that would fulfil my curiosity and passion for learning would be a career in research. Having realised that, biology was a natural choice for me.

And what about art – have you always enjoyed it?

Absolutely yes. Drawing is the thing that I remember loving ever since I was a child. I was always drawing my favourite characters from comics, books or movies and even more from my imagination. At some point I really wanted to become a comic book illustrator!

What or who are your artistic influences?

I think my drawing “style”, so to speak, owes a lot to the Disney comics I used to read in my childhood/teenage years and more generally to the visual aesthetics of cartoons and anime from the 90s. I also deeply love fantasy literature and often draw characters and scenery from books, with The Lord of the Rings being my main inspiration above all.

Speaking of scientific illustrations, one of the artists I admire the most is David Goodsell. I find his way of drawing the crowded interior of a cell so elegant and thought-provoking!

Neutralising antibodies fighting against SARS-CoV2.

How do you make your art?

Nowadays I mostly use digital media for my illustrations. Digital art is truly amazing, it offers so many opportunities and I have just scratched the surface of its potential. When I approach a new artwork I usually spend most of the time thinking about the message I want to convey. If I am working for someone else I try to grasp the main scientific concepts and do a bit of research to see how people typically represent that something. Once I have a rough idea of what I am aiming for, I move to the actual painting. I find it somewhat liberating to stare at the white canvas and just go with the flow, without knowing what the final result will look like. It’s a nice contrast with my daily routine as a researcher, where everything is much more schematic and there is no room for improvisation. Nonetheless, in my view science is also a creative process. Thinking outside the box to formulate new hypotheses or devising innovative technologies requires some degree of creativity, so the two worlds are not so far apart.

I find it somewhat liberating to stare at the white canvas and just go with the flow

Co-co assembly: a novel mechanism of co-translational assembly of protein complexes (reference: Bertolini et al., 2021, Science)

Does your art influence your science at all, or are they separate worlds?

Finding a way to combine my creativity and my scientific education has definitely helped me to grow as a scientist and also consolidated my enthusiasm for research. First, having this side-project has helped me to balance out a lot of the stress during the final years of PhD. It was very important to have my own happy place to switch the brain off and recharge batteries. Secondly, I like thinking about scientific concepts without constraints and just letting my imagination go. It’s a different approach to science, as I don’t have to be rigorous but I can just take the main facts and shift them into a new perspective. I enjoy having my imagination take the lead and drawing without strictly adhering to canonical imagery. At the end of the day, doing this makes me even more fascinated by the wonders of biology!

Uropathogenic E.coli binding to Uromodulin filaments via their pili (reference Weiss et al. 2020, Science)

What are you thinking of working on next?

I don’t have a clear plan of where I’m going with my scientific illustrations, but I definitely want to perfect my skills in digital painting and challenge myself with something new, like animation or 3D. Communicating science to peers and public is something I deeply care about, so I’m hoping that my illustrations can help people come closer to biology.

Marzia’s animation of a mouse zygote dividing

Check out Marzia’s website www.munafomarzia.com and Twitter page https://twitter.com/munafomarzia

We’re looking for new people to feature in this series throughout the year – whatever kind of art you do, from sculpture to embroidery to music to drawing, if you want to share it with the community just email thenode@biologists.com (nominations are also welcome!).

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Development presents… May webinar

Posted by , on 29 April 2021

 

Wednesday 12 May 2021 – 16:00 BST (GMT+1)

The eighth webinar in our Development presents… series will be chaired by Development Editor Paola Arlotta (Harvard Stem Cell Institute), who has invited three exciting talks on the topic of mammalian brain development.

 

Tian Tian (formerly a PhD student in David Price’s lab and now a postdoc in Matthew Nolan’s group at the University of Edinburgh)
‘Pax6 regulates the morphological and electrophysiological development of mouse prethalamic neurons’

 

Li He (PhD student in Qi Dai’s lab at Stockholm University)
‘Transcription factor PRDM16 promotes temporal progression of cortical neural stem cells’

 

Karol Kaiser (formerly a postdoc in Vitezslav Bryja’s lab at Masaryk Univeristy now a postdoc in Fiona Doetsch’s lab at the University of Basel)
‘Meis1-Wnt5a axis – The story of two choroid plexuses’

 
 

The webinar will be held in Remo, our browser-based conferencing platform. After the talks you’ll have the chance to meet the speakers and other participants at virtual conference tables. If you can’t make it on the day, talks will be available to watch after the event on the Node. You can also sign up to our mailing list for email alerts.

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Sperm development linked to testicular cancer

Posted by , on 28 April 2021

A Press Release from Development

Scientists led by Dr Jason Heaney from Baylor College of Medicine in Texas, USA, have found that a failure in the development of sperm cells can lead to the formation of testicular tumours in mice. These findings, published in the journal Development, provide new clues for understanding how testicular cancer arises in mammals.

Testicular cancer is the most common type of cancer to affect men between the ages of 15 and 49, and around 95% of these cases are caused by testicular germ cell tumours. Although testicular germ cell tumours typically manifest after puberty, problems in the embryonic development of germ cells can transform them into cancer cells that form tumours later in life.

In the embryo, germ cells initially have the potential to form many different cell types, a characteristic called pluripotency. Normally, germ cells lose this ability as embryonic development progresses and they become restricted to only form sex cells – sperm in males and eggs in females – in a process known as sex determination. Male sex determination also coincides with the embryonic period when the cancer cells that form testicular germ cell tumours can develop.

As Dr Jason Heaney, Associate Professor at the Department of Molecular and Human Genetics at Baylor College of Medicine revealed, the timing between cancer cell formation and sex determination is more than just coincidental: “previous work from our lab and others indicated that defects in this sex-specific switch may play a central role in facilitating the initiation of testicular germ cell tumours. In this study, we set out to test whether testicular germ cell tumours arise from germ cells that do not begin the sex-specific differentiation process and retain features of pluripotent cells.”

To test this hypothesis, Dr Heaney together with Dr Nicholas Webster and team explored whether a gene called Nanos2, which is needed for sex-determination, also prevented embryonic cancer cells developing in mice. “NANOS2 plays a key role in the sex-specific development of embryonic germ cells by suppressing the female (egg) fate and promoting the male (sperm) fate,” explained Dr Heaney.

Using a strain of mice that spontaneously develop germ cell tumours, the researchers showed that some germ cells lacked NANOS2. Not only did the NANOS2-deficient germ cells fail to mature into sperm, but they remained pluripotent and, crucially, were more likely to transform into embryonic cancer cells. The scientists also characterised the NANOS2-deficient germ cells and uncovered important changes in cell behaviour, which could be used to identify and treat cancer cells in the future. “Our work reveals changes in gene expression when germ cells transform into cancer cells that suggest alterations in metabolism and cell division, which could be used for targeted therapies,” said Dr Heaney.

Although it is currently unclear what role NANOS2 plays in the development of human testicular germ cell tumours, this study highlights an important link to the process of male sex determination, providing a new direction for future research. “Our studies provide functional evidence for a mechanism – disrupted male germ cell fate determination – through which these genes cause testicular germ cell tumours in humans,” said Dr Heaney, “future studies will use genetically modified mice to explore how genes associated with germ cell tumours in humans influence germ cell transformation.”


Webster, N. J., Maywald, R. L., Benton, S. M., Dawson, E. P., Murillo, O. D., LaPlante, E. L., Milosavljevic, A., Lanza, D. G. , Heaney, J. D. (2021). Testicular germ cell tumors arise in the absence of sex-specific differentiation. Development, 148, dev197111. doi:10.1242/dev.197111

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Circadian clock in the mouse placenta

Posted by , on 28 April 2021

This press release was released by Development (paper link).

The placenta forms the interface between the maternal and foetal circulatory systems. As well as ensuring essential nutrients, endocrine and immunological signals get through to the foetus to support its development and growth, the placenta must also protect it from the accumulation of potentially toxic compounds. A study from Cécile Demarez, Mariana Astiz and colleagues at the University of Lübeck in Germany now reveals that the activity of a crucial placental gatekeeper in mice is regulated by the circadian clock, changing during the day-night cycle. The study, which has implications for the timing of maternal drug regimens, is published in the journal Development.

Immunofluorescence reveals that the ABCB1 protein (in green) localises to the labyrinth zone of the mouse placenta.

The circadian clock translates time-of-day information into physiological signals through rhythmic regulation of downstream genes. In this study, the researchers discover that in the labyrinth zone of the mouse placenta, a tissue functionally equivalent to the human chorionic villi, clock genes are expressed in a 24h rhythm. Importantly, they show that this placental clock is responsible for regulating the expression and activity of ABCB1, a drug efflux transporter with hundreds of known substrates.

An important prediction of this work is that the time-of-day of maternal treatment could be an important factor to consider to avoid non-desirable effects for the foetus during pregnancy.

“Pharmacological treatments are mostly avoided by pregnant women but in certain circumstances there is no other option,” says Dr. Mariana Astiz. “An example would be maternal treatment with antiretrovirals (many of which are in fact substrates of ABCB1). So, choosing the correct time of day to take drugs like these might reduce the ammount of drug reaching the baby and hence the possible negative effects in the short and long-term.”

Dr. Astiz hopes this study will provide a stimulus to design studies that specifically test hypotheses about the placental circadian clock in humans. “This is definitely a very exciting and rapidly advancing field of research.”

The trophoblast clock controls transport across placenta in mice

Cécile Demarez , Leonardo Vinicius Monteiro De Assis , Markus Krohn, Nahuel Ramella , Markus Schwaninger , Henrik Oster, Mariana Astiz. Development (2021) 148 (8): dev197673.

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#DevBiolWriteClub, Post #4

Posted by , on 24 April 2021

When I wrote the #DevBiolWriteClub rules, I made Rule #2 simply restate Rule #1.  This, of course, was a cheap ploy by the author to make the reader compare him favorably to Brad Pitt.  But there is a serious intent behind it. 

Becoming a better writer takes dedication and it takes hard work, but mainly it takes patience.  Let’s imagine you read my first post on the Node last Spring, or that you’ve been allowing me to hector you on Twitter.  By now, you’ve put a year of effort into developing your craft as a writer.  Seen any impact yet?  Perhaps you’ve got more words down on the page, or maybe you’re a bit more pleased with your writing.  Maybe, but it’s more likely that any progress you’ve made is pretty much intangible at this point.  That’s the nature of writing, and it’s a major part of why it is such a frustrating endeavor.

But trust me, simply practicing is by far the best thing you can do for your writing.  If you have an active project, try to write at least a little every day.  If you are between writing projects, read more and take the time to notice the writing while you read it.  That said, there’s no question that we all hit a wall sometimes.  Learning to get some outside help is critical.    

Thus, we finally come to Rule #5: You can’t do it alone. 

Now, getting help can take two forms.  The simpler way is to read books about writing.   Notice that I said “books,” plural.  I wrote about this in my last post, so I won’t repeat it here, except to say there are LOTS of great books about writing.  Go read them.  But also know that no book will ever do for you what an engaged reader can do, so let’s talk about the real meat of Rule #5.  Show your work to others and get their feedback.

Many years ago, Frank Conlon sent me a great essay in The New Yorker by Atul Gawande.  The essay pointed out that essentially all professional athletes will be coached throughout their entire careers, as will most opera singers.  But surgeons aren’t.  Scientists aren’t, either.  So, you need to nurture your own stable of informal coaches

It turns out that I am both lazy and ambitious.  It’s an odd combination but it has made me very good at asking for help.  In terms of writing, getting help started early.  One of my first “coaches” was Mr. Mike Cullinan, an English teacher loved and feared by generations of students at my high school in Houston.  He once gave me a 10 on a paper.  Out of 100, yes.  You see, he graded content and writing separately and averaged the scores.  Various transgressions of grammar or diction had fixed point values (25 points for each run-on sentence).   So, despite a high score for content, I had scored a negative 75 for writing.  I had to re-write it.  I had to re-write most things I wrote for him.  And you know what?  The writing always got better.  Every single time.

By the time I became a PI, I had become religious about seeking advice on anything I write.  I actually got the first R01 grant I applied for as a PI.  (It was fun to briefly boast of my 100% NIH success rate, but the euphoria was short-lived; I didn’t get the second one.)   What’s important to understand, though, is that I spent an entire year writing that grant.  Of course, I also had to order equipment, hire people, and go to new faculty orientation.  But I worked on the grant, bit by bit, most days.  For a year.  I revised and revised and revised.  Along the way, that one grant application took in the serious feedback of five faculty members, three developmental biologists (Richard Harland, Paul, Krieg, David Parichy) and two cell biologists (Terry O’Halloran, Arturo De Lozzane).  It was an awesome learning experience and it generated one of the tightest pieces of grant writing I’ve ever produced.    

As I have aged, I find myself more lazy than ambitious, and I sometimes submit writing that no one else has read.  It almost always goes badly.  Luckily, however, old habits die hard, and I still usually seek input from an outside reader. I wrote an essay in Developmental Cell in 2019. that is probably my favorite piece of writing.   But let me tell you, it started poorly.  I sent an early draft to Lila Solnica-Krezel, and her response was something like, “Oh, you can’t possibly think of publishing this!  It’s awful!”  She was absolutely correct.  You see, I knew what I wanted to say.  It was clear in my head.  But the points were wholly lost on my reader.   Clearly, I was not yet able to say what I wanted to say.  I went back to work, started almost entirely from scratch.  It was over a year before I completed the essay and sent it off.  Then, I was lucky enough to have Marie Bao handle the essay as Editor at Dev. Cell.  She liked the idea and found it important, but the essay needed work.  Entire sections had to be cut, other shad to be focused, still others expanded.  We went back and forth through several rounds of revision.  When the piece was finally published, I was proud of it and I was even more delighted that it was well-received.  But honestly, it was a team effort. 

I tell this story because it illustrates perhaps the most important and most challenging part of getting feedback on your writing.  You have to do it early.  The key mistake I see writers make is to wait until the very final stages to get feedback.  They want to give their reader a “polished draft,” usually because they are concerned about what the reader will think of their rough work.  This presents a host of problems:

First, by the time you’re in the final stages, there is often very little time to make serious revisions.  Edits of spelling and grammar, sure; but real change?  If you read a friend’s grant that is due in 48 hours and your thought is that all of Aim 1 sucks, what do you do?  You correct the typos and perhaps utter a small prayer.   You certainly don’t say “replace all of Aim 1.”   But what if you had seen that grant three weeks before it was due?   Now, it’s true that papers do not come with deadlines, but let’s be honest:  Every piece of writing has an expiration date, as the author’s patience with the project inevitably wanes.

Second, by the time you have gotten to what you consider is a polished draft, you obviously like it!   And, simply because of the cumulative effect of effort, the more work you put into a piece of writing, the more invested you become.  This creates a fatal problem:  the longer you wait for feedback, the less you will be willing to change, the less likely you will be to really listen to feedback.

Finally, a more subtle point.  If you wait until the end of the process, you will get editorial feedback, but you’ll learn nothing about your craft as a writer.  This is especially important for trainees showing their work to mentors.  Given the greater experience, your mentor is very likely the better writer.  Thus, by sharing your very rough work early in the process, you can get feedback not just on what you’ve written, but also on your writing process.  And remember, like it or not, you are a writer, and you need to be serious about getting better at your craft.

So that’s it.  Toughen up and show your writing, however rough or embarrassing, to other people and get their feedback.  It’s uncomfortable, but it really, really works.

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An interview with Wajid Jawaid, 2020 BSDB Beddington Medal Winner

Posted by , on 22 April 2021

The Beddington Medal is the British Society for Developmental Biology’s major commendation to promising young biologists, awarded for the best PhD thesis in Developmental Biology defended in the year previous to the award.

 The design of the medal, mice on a stylised DNA helix, is from artwork by Rosa herself.

In 2020 the Beddington Medal was awarded to Wajid Jawaid, who did his PhD with Berthold Göttgens and Jenny Nichols at the Wellcome-MRC Stem Cell Institute, University of Cambridge. After the cancellation of the spring meeting in 2020, Wajid is going to present his work today at the BSDB/Genetics Society 2021 meeting, right before the 2021 winner (who we’ll also interview soon). In advance, we caught up with Wajid to find out more about his life in science. Be sure to also check out the profile of Wajid – including words from Jenny Nichols and a list of Wajid’s selected publications – over on the BSDB site.

Where were you born and where did you grow up?

Birmingham is my home town and where I was born and schooled. My family are still there and I love visiting regularly.

When did you first get interested in science?

I’ve always been interested in how things work since as far back as I can remember and have had a keen interest in science since school. My eyes were really opened during my first year at University in Aberdeen when I found the treasure trove ‘Pubmed’ during a special study module on road traffic accidents. I couldn’t believe the amount of information that was freely available to anyone with an internet connection.

You came into your PhD from paediatric surgery – why did you decide to move into research, and why with Berthold Göttgens and Jenny Nichols in particular?

I became interested in paediatric surgery after my elective at British Columbia Children’s Hospital in Vancouver which exposed me to rare congenital anomalies and their surgical correction or at least amelioration. The process of reading and learning about the embryology that forms the basis of normal development and how it can go wrong consolidated my interest and I decided I wanted to become a Paediatric surgeon.

My interest in science and embryology drove me to apply for an Academic Clinical Fellowship (ACF) post in Paediatric Surgery based at Alder Hey hospital. There I met two wonderful mentors Professor Paul Losty and Mr Edwin Jesudason. As part of my ACF I visited Dr Emma Rawlin’s lab at the Gurdon Institute. This was my first exposure to lab based research and I soon became aware of the importance of integrating multiple and large sources of data. At the time I also became aware of Professor Jenny Nichol’s work in early embryogenesis, embryonic stem cells and pluripotency.

The Wellcome Trust kindly agreed to allow me to extend my PhD by taking 1 year to do a MPhil in Computational Biology at the Department of Applied Mathematics and Theoretical Physics co-ordinated by Dr Stephen Eglen and Dr Boris Adryan. This was a critical year that gave me the skills that I would use through-out my PhD. During the MPhil I attended a talk given by Professor Bertie Gottgens where he presented his most recent dataset and the concept of computational reconstruction of a pseudo-time developmental trajectory from single cell resolved qPCR data. I approached him and together we developed a project with Professor Jenny Nichols.

Tell us about your PhD project: what were the main questions you were trying to answer?

The development of new technologies allowing application of ‘-omics’ methods to single- cells was paving the way to understanding cell biology at much higher resolutions than previously possible. One application was in elucidating the journey of a progenitor cell as it became sequentially fate restricted until it finally reached its destination cell type. Despite the advances in technology it had not been possible to follow this journey across all genes/transcripts over time in-vivo. Single cell RNA sequencing was in its infancy but had the potential to achieve computational reconstructions of these journeys if single cells could be harvested from mouse embryos and retain their transcriptome. At the time it was not clear whether single cell transcriptomic data could be gathered at sufficient precision from dissociated embryos to allow cell type identification and lineage reconstruction.

The overarching theme of this body of work was to develop methods to reconstruct ordered ontogenic trajectories through sequentially sampled cross-sectional data at gastrulation in mice. The main focus was using single-cell resolved, transcriptomic data collected during early mouse embryonic development. Where available this was supplemented with limited, hand selected cell surface proteomic measurements.

The main aims were: 1. Identify cell populations; 2. Trace biologically plausible trajectories; 3. Identify novel molecular pathways; and 4. Develop models that can faithfully simulate cell progression along trajectories

This method of lineage reconstruction best fitted with retrospective lineage tracing. Lineages were traced based on the assumption that within a window of developmental time, cells with the most similar transcriptional signatures were related by lineage.

And what do you think your key discoveries were?

Our first experiment was to take early mouse embryos at gastrulation at four time points between E6.5 and E7.75. In the 3 later time-points cells were sorted to select for Flk1+ or CD41+ mesodermal cells using and An early key finding was that single cell resolved embryonic cell type could be accurately determined. Having identified cell types we were able to the identify sub-populations within the endothelial cluster and focus our analysis on a set of genes associated with erythromyeloid progenitors. In this way we were able to identify the activation of the leukotriene branch of the arachidonic acid pathway within this subset of endothelium. This reminded me of biochemistry from my pre-clinical years and its association with asthma so I was easily able to recall an inhibitor Zileuton. We went on to validate its role in haematopoiesis in an in vitro model of haematopoiesis. Another interesting observation Zileuton itself a derivative of hydroxyurea induces foetal haemaglobin and may have a role in the treatment of sickle cella anaemia. This finding then potentially suggests the mechanism of action of Zileuton.

Given advances in stem cells and organoids, what do mice still have to tell us about early mammalian development?

There have been great achievements in stem cell biology and organoids but they are still a long way off the gold standard the developing embryo which can at relatively high efficiency develop from a single cell to a recognisable organism with cells arranged in functional organ units. This complex process can not yet be faithfully recapitulated in any stem cell or organoid system.

By studying this process in nature we may be able to adjust our culture systems to improve the fidelity of both stem cell and organoid models of normal physiology and disease.

If you took one abiding memory with you from your PhD, what would it be?

Progress through a PhD is full of ups and downs. The moment that I am most fond of is when I was developing a neural network to model a bifurcating developmental trajectory to endothelial and blood fates. This had worked very well compared to a linear regression model. To test it, I wanted to perform a gene knock-out in Tal 1 which should have resulted in failure in erythroid generation. Unfortunately this was not working and I was ready to change tact when I realised I was dealing with qPCR data where activation was associated with a low cycle count – in my case it meant for knockout I should have been using a value of 14 rather than zero. When I corrected this error the network finally reproduced the experimental findings.

What are you doing post-PhD?

At the moment I have focused on completing clinical training. In the meantime I am also preparing to apply for a post-doc clinical fellowship to combine clinical and research work. My aim in the long term is to combine both research and clinical work. Clinical work often raises questions and challenges providing important research questions.

Where do you think developmental and stem cell biology will be in ten years?

I hope we will capture more the complex interactions and higher order abstractions of these interactions beyond pathways, linking the genome and its structure to function and anatomy. In 10 years, I hope that we are at the stage where our understanding of the information in the genome and the functional modules is sufficient to not only describe how organs develop but also how we can make changes to the programs of development to prevent disease phenotypes. So that in time, rather than disrupting development we can generate our own programs de novo.

Integration of multi-omics data with spatial context may help us move from the concept of differentiating a stem cell to more committed fates to generating complex structures of multiple cell types that can be used as substitutes for organs without artificial or de-cellularised scaffolds. Some organoid systems are already taking an early step in this direction.

When you’re not in the lab, what do you do for fun?

Over the last few years through my children going to a football club, I have become a volunteer coach at this local football club. More recently I’ve got my self a motorbike which I love to ride and fix up.

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Genetics Unzipped podcast: Making better medicines – unlocking the promise of genomics for drug discovery

Posted by , on 22 April 2021

National Cancer Institute, CC0 via Unsplash

In the latest episode of Genetics Unzipped we’re finding out how researchers are unlocking the information hidden within the human genome using new technologies like CRISPR gene editing and artificial intelligence with the aim of developing better medicines and getting them faster to the patients who need them.

Genetics Unzipped is the podcast from The Genetics Society. Full transcript, links and references available online at GeneticsUnzipped.com.

Subscribe from Apple podcasts, Spotify, or wherever you get your podcasts.

Head over to GeneticsUnzipped.com to catch up on our extensive back catalogue.

If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip

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Out on a Flimb or: How I Learned to Stop Worrying and Trust the Mapping

Posted by , on 20 April 2021

Recently we reported the unexpected ability of fish mutants to develop limb-like bones in their pectoral fins (Hawkins et al., 2021). However, the most critical element of the study—finding these mutants in the first place—receives relatively little attention in the paper. Here I describe our efforts to find these monsters lurking inside the unassuming zebrafish.

The nuts and bolts of fins and limbs

The transition from fins to limbs is a defining transformation in vertebrate history and has served as a pivotal study system for comparative anatomy, paleontology, biomechanics, and developmental biology (Clack, 2009). Insight from each of these fields has illuminated different facets of how a relatively simple ancestral fin evolved into the complex arms and legs of tetrapods. Modern fins and limbs look quite different from one another but revealed in the fossil record are intermediate forms that connect their disparate morphologies (Jessen, 1972; Shubin et al., 2006; Zhu and Yu, 2009). By comparing the gene programs active in fins and limbs, we can ask which patterning mechanisms are common to both appendages, which mechanisms are derived in each, and which could be responsible for the changes in form found in evolution.

Tetrapod limbs have many long bones that articulate end on end away from the shoulder with distinct regions such as the upper arm (humerus), forearm (radius and ulna), and hand (Figure 1). In contrast, the pectoral fins of teleost fishes have just four long bones set side by side (proximal radials) followed distally by some small nodular bones (distal radials) and the dermal fin rays (Arratia, 1999). Non-teleost ray-finned fishes such as the bowfin have a slightly more impressive endoskeleton with additional articulations in the posterior part of the fin. Paleontological evidence suggests that the common ancestor of ray-finned fishes and tetrapods had a pectoral configuration much like that of the bowfin (Jessen, 1972, Zhu and Yu, 2009). In this scenario, teleosts such as the zebrafish represent a reduction of the ancestral appendage skeleton, while limbs exhibit its impressive elaboration (Coates, 1995).

Figure 1. Pectoral appendage anatomy is variable across the bony fishes. From the ancestral configuration that exhibited moderate elaboration in the posterior fin (bottom), teleosts (left) simplified the endoskeleton such that it consists of a row of proximal radials followed by small nodular distal radials. In contrast, in the lineage leading to tetrapods (right), the fin was elaborated through the addition of distal long bones to form a limb with a three-part structure containing the upper arm (humerus), forearm (radius and ulna), and hand (wrist and digits). Anterior to left, distal to top in skeletal schematics.

Forming an impressive body of work spanning the last four decades, developmental geneticists across the globe have discovered and characterized the manifold genes and pathways that control the growth and patterning in the nascent limb, leading to a deep understanding of the signaling ligands, receptors, and transcription factors necessary to make a normal appendage (Capdevila and Izpisúa Belmonte, 2001). Surprisingly, despite the morphological differences, many of these key limb patterning pathways are also expressed in developing teleost fins and play analogous (or conserved) functional roles (Mercader, 2007). There are differences in the expression and signaling function of some of these important players, but on the whole fin buds and limb buds behave quite like one another, and there is not one clear genetic factor present in limbs and absent in fins that is sufficient to imbue ‘limb-ness.’

Fishing for fin mutants

While assessing the role of candidate limb genes in growing fins has yielded critical insights into fin development, my colleagues Katrin Henke, Matthew Harris, and I decided to investigate the genes that can modify the zebrafish fin pattern using forward genetics. In a forward genetics approach, mutations are made at random and the investigator screens through mutated animals to pick out individuals with an interesting phenotype (Patton and Zon, 2001). Once an interesting mutant is found, we then work backwards using genetic mapping to determine which gene was mutated to cause the phenotype. The beauty of forward screens is that they let the organism tell you which genes are important to the process you want to know about. Sometimes you find an allele of a known essential regulator that has been extensively characterized, other times you find a gene that hasn’t been studied at all.

Katrin conducted several prodigious screens with a focus on mutants that affect the formation of the adult skeleton, and isolated hundreds of novel mutants (Henke et al., 2017). One mutant she picked out because of its modified pigmentation and dysmorphic fin rays was of particular interest to me and Matthew. Upon observing the internal skeleton under the dissecting scope, Matthew saw that the fin endoskeleton was affected and suggested I take a look. Shockingly, instead of having just the four long bones set side by side, this mutant had additional long bones forming in the distal endoskeleton that articulated with the proximal elements with a joint analogous to an elbow (Figure 2). This mutant didn’t just have fins, but what it had were not quite limbs either: it grew “flimbs.” At the time my dissertation project was focused on craniofacial mutants, but after this discovery (and Katrin’s blessing) my focus shifted to this fascinating mutant with limb-like fins. All good mutants need a name, and my friend and Old Testament scholar Maria suggested rephaim, a race of biblical giants fabled to have extra digits on their hands and feet.

Figure 2. Novel long bones form in the distal endoskeleton of rephaim mutants. Top panels show the external appearance of wild-type and rephaim mutant fish. Middle panels contain micrographs of pectoral fins stained red for bone and blue for cartilage. The proximal radials are numbered 1 through 4, and the new bones in the mutant are indicated with an asterisk. Bottom panel schematizes the endoskeletons of wild-type and ­rephaim fins and indicates the position of the intermediate radials and novel joint in the rephaim mutant.

After receiving a name, mutants need to be mapped to determine which gene is affected. Genetic mapping of mutations used to be a long and involved process using chromosomal markers to track linkage and recombination. In early zebrafish screens, a mutant line would be crossed to a wild-type fish from a different genetic background, and PCR-based methods would be used to find variable genomic positions and track down regions of DNA that segregated with the mutant phenotype (Knapik et al., 1996). In the last 15 years, however, the advent of next-generation sequencing made it possible to sequence mutants and their wild-type siblings to quickly identify genomic regions that associate with the mutant phenotype. To map rephaim, we utilized a whole-exome mapping approach to determine genomic regions that likely contain the causative mutation (Bowen et al., 2012). The mapping data gave us two putative regions that could contain the rephaim mutation, one on chromosome 4 and one on chromosome 9. Chromosome 4 has a reputation as being a nightmare for mapping, replete with inversions and transposons, and the implicated interval didn’t contain any interesting limb patterning genes. I did not like chromosome 4. On the other hand, the interval on chromosome 9 contained the HoxD cluster, a battery of genes with critical roles in appendage patterning and particularly implicated in the differential patterning of fins and limbs (Sordino et al., 1995; Freitas et al., 2012; Woltering et al., 2014). Not only would a mutation in a HoxD gene fit my expectations of what could cause a phenotype like rephaim, it would make subsequent analysis of the mutant phenotype much easier and fit well within the existing fin-to-limb literature. I even thought I might finish my dissertation early.

This, however, was not to be. Linkage analysis definitively ruled out chromosome 9 and the HoxD cluster. The initial mapping signal that I had pinned my hopes on was due to a block of genetic homogeneity that was shared between mutants and wild-type siblings, meaning that both mutants and wild-type animals had the same alleles in this region and thus could not contain the causative mutation. Meanwhile, additional recombination analysis strengthened the association of rephaim with chromosome 4 and narrowed the linkage interval to a small window containing just one coding mutation in a gene called wiskott-aldrich syndrome protein like-b (waslb). Unlike my precious HoxD cluster, the waslb gene was not a known regulator of limb development, and everything I saw in the literature gave the impression that it was a “housekeeping” gene: ubiquitous expression, essential functions in actin metabolism, and involvement in myriad cellular pathways (Snapper and Rosen, 1999). Around this time, we were also mapping a second mutant with a similar phenotype, a fish called wanda (van Eeden et al., 1996; Haffter et al., 1996). The causative mutation for wanda mapped to the gene vav2, a similarly unexciting locus from a skeletal patterning perspective (Hornstein et al., 2004). I felt the path to my PhD lengthening in real time.

X marks the spot on a genetic treasure map

Nevertheless, all the mapping data pointed to waslb and vav2, so these genes demanded our attention. Mapping implicated these genes, but we still needed to experimentally confirm their role in the flimb phenotype. We used CRISPR-Cas9 to make loss-of-function alleles, but even homozygous null mutants had a wild-type phenotype (Figure 3). Next we tried injecting mutant mRNA into the embryo but saw no effect, likely due to the late appearance of the phenotype. In a final push to demonstrate the causative nature of the waslb and vav2 mutations, we used CRISPR to create frameshift lesions in cis to the candidate mutations and knockout the mutant alleles specifically. When the mutant copies of waslb and vav2 were removed, we rescued the phenotype and reverted the mutants to wild-type fin patterning. There was no doubt, mutations in waslb and vav2 cause the flimb phenotype. But this left us with a bigger question, how in the world are these genes changing skeletal patterning? I came up with an axiom to sooth myself: “if good science raises more questions than it answers, then the best science must raise only questions and answer nothing.

Figure 3. Rescue experiments demonstrate that a mutation in waslb causes the rephaim phenotype. CRISPR-Cas9 was used to generate null alleles in wild-type and rephaim mutant waslb. Removing wild-type alleles (waslbΔ) had no effect on fin patterning. However, creating a frameshift and early stop upstream of the S265P mutation (waslbΔ+ reph) prevented the formation of intermediate radials and rescued wild-type patterning.

However, the wealth of limb patterning knowledge established by developmental geneticists was able to guide our inquiry. As mentioned earlier, Hox genes have critical functions in the patterning and growth of limb bones along the proximal-distal axis, and recent studies had revealed that Hox13 was required for the formation of the most distal structures in fins just like in limbs (Nakamura et al., 2016). We thought that the new bones in rephaim might also share this distal Hox13 regionality, and crossed rephaim into a Hox13-null genetic background. To our surprise, we found that loss of Hox13 actually enhanced the flimb phenotype and resulted in the formation of even more bones along the distal aspect of the endoskeleton (Figure 4). Hoxa13 is known to negatively regulate Hoxa11 expression in the limb (Kherdjemil et al., 2016), and we thought the enhanced phenotype might be the result of derepression of Hox11 genes. Around this time we also were analyzing limb-specific Wasl knockout mice, and observed limb defects similar to those seen in Hoxa11 mouse mutants. Intriguingly, Hox11 genes are also required for the normal development for the bones in the middle region of the limb, the radius and ulna (Davis et al., 1995).

Figure 4. Genetic interaction between rephaim and Hox genes suggests limb-like patterning mechanisms function in the fin. While loss of hoxa11a, hoxa11b, and hoxd11a has no effect on fin patterning in the wild-type background, removal of these genes prevents the formation of intermediate radials in rephaim mutants. In contrast, removing hoxa13a and hoxa13b from rephaim mutants enhances the phenotype and results in the formation of additional intermediate radials. The requirement of Hox11 genes is shared between intermediate radials and the limb forearm.

Following these clues, we generated null alleles of the hoxa11 and hoxd11 paralogs in the zebrafish. While loss of these genes had no effect on fin patterning in a wild-type background, we found that loss of hoxa11a and hoxa11b prevented the formation of the extra bones in rephaim mutants (Figure 4). Moreover, we generated knock-in hoxa11b reporter zebrafish and found that rephaim and wanda mutants cause the upregulation of hoxa11b expression. These results were quite interesting: even though the Hox11 paralogs are not required for normal fin patterning in zebrafish, they still possess the ability to specify the formation of an intermediate long bone position along the proximal-distal axis of the appendage skeleton. This suggests that the capacity to specify ‘middle’ and ‘distal’ regions is not unique to limbs, but was present in the common ancestor of ray- and lobe-finned fishes. Although not expressed in teleosts, this developmental potential has been retained in a latent state and can be redeployed by simple perturbations.

Wasl, Hox, and Beyond

This forces me to wonder what other latent limb patterning mechanisms that might reside in the developing fin bud, and how waslb is able to activate at least some of them. The mechanistic connection between waslb, vav2, and Hox regulation is an open question. In part, we know that waslb mediates the formation of F-actin foci that colocalize with Hox-positive cells in the distal fin (Hawkins et al., 2021). Given its roles in cell motility it could be that waslb effects the migration of these cells, but there are many other possibilities. Wasl also directly regulates transcription (Wu et al., 2006), modulates Wnt (Lyubimova et al., 2010) and TGFB (Lefever et al., 2010) signaling, and is directly involved in the colinear activation of the HoxB cluster (Ferrai et al., 2009). Then again, there could be another pathway that we do not yet understand. I will go out on a flimb here and say the zebrafish still has more to tell us about these mechanisms…as long as we are willing to trust the mapping.

For further reading, you can find our published manuscript at https://www.cell.com/cell/fulltext/S0092-8674(21)00003-9

You can also see an explainer thread on Twitter at https://twitter.com/Homeobox/status/1357382005261017098?s=20

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