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

This month evo-devo is particularly well represented (from choanoflagellates to Portuguese men of war), and there’s a slew of single cell sequencing papers, lots on iPSC differentiation and some rooting around in our plant development section.

The preprints were hosted on bioRxiv, PeerJ, and arXiv. Let us know if we missed anything, and use these links to get to the section you want:

Developmental biology

| Patterning & signalling

| Morphogenesis & mechanics

| Genes & genomes

| Stem cells, regeneration & disease modelling

| Plant development

Evo-devo & evo

Cell biology

Modelling

Tools & resources

Research practice & education

Developmental biology

| Patterning & signalling

C. elegans Runx/CBFβ suppresses POP-1(TCF) to convert asymmetric to proliferative division of stem cell-like seam cells
Suzanne E. M. van der Horst, Janine Cravo, Alison Woollard, Juliane Teapal, Sander van den Heuvel

A direct glia-to-neuron natural transdifferentiation ensures nimble sensory-motor coordination of male mating behaviour
Laura Molina-García, Byunghyuk Kim, Steven J. Cook, Rachel Bonnington, Jack M. O’Shea, Michele Sammut, Sophie P. R. Gilbert, David J. Elliott, David H. Hall, Scott W. Emmons, Arantza Barrios, Richard J. Poole

Patterned cell death sculpts functional and adaptive neural networks in flies
Sinziana Pop, Chin-Lin Chen, Connor J Sproston, Shu Kondo, Pavan Ramdya, Darren W Williams

Functional divergence of Plexin B structural motifs in distinct steps of Drosophila olfactory circuit assembly
Ricardo Guajardo, David J Luginbuhl, Shuo Han, Liqun Luo, Jiefu Li

Metabolic adjustment of Drosophila hemocyte number and sessility by an adipokine
Elodie Ramond, Bianca Petrignani, Jan Paul Dudzic, Jean-Philippe Boquete, Mickaël Poidevin, Shu Kondo, Bruno Lemaitre

Sir2 non-autonomously controls differentiation of germline cells in the ovary of Drosophila melanogaster
Champakali Ayyub, Ullas Kolthur-Seetharam

Electron transport chain biogenesis activated by a JNK-insulin-Myc relay primes mitochondrial inheritance in Drosophila
Zong-Heng Wang, Yi Liu, Vijender Chaitankar, Mehdi Pirooznia, Hong Xu

Mesenchymal-Epithelial Transition Regulates Initiation of Pluripotency Exit before Gastrulation
Sofiane Hamidi, Yukiko Nakaya, Hiroki Nagai, Cantas Alev, Takeya Kasukawa, Sapna Chhabra, Ruda Lee, Hitoshi Niwa, Aryeh Warmflash, Tatsuo Shibata, Guojun Sheng

Neuromesodermal progenitors separate the axial stem zones while producing few single- and dual-fated descendants
Timothy R. Wood, Anders Kyrsting, Johannes Stegmaier, Iwo Kucinski, Clemens F. Kaminski, Ralf Mikut, Octavian Voiculescu

Modeling binary and graded cone cell fate patterning in the mouse retina
Kiara C. Eldred, Cameron Avelis, Robert J. Johnston Jr., Elijah Roberts

Cis-regulatory basis of sister cell type divergence in the vertebrate retina
Daniel Murphy, Andrew. E.O. Hughes, Karen A. Lawrence, Connie A. Myers, Joseph C. Corbo

RNF152 Negatively Regulates mTOR Signalling and Blocks Cell Proliferation in the Floor Plate
Minori Kadoya, Noriaki Sasai

Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function
Jonathan Alevy, Courtney A. Burger, Nicholas E. Albrecht, Danye Jiang, Melanie A. Samuel

Neuronal Activity Enhances mRNA Localization to Myelin Sheaths During Development
Katie M. Yergert, Jacob H. Hines, Bruce Appel

Thyroid hormone coordinates developmental trajectories but does not underlie developmental truncation in danionins
Yinan Hu, Angela Mauri, Joan Donahue, Rajendra Singh, Benjamin Acosta, Sarah McMenamin

Endocardial differentiation in zebrafish occurs during early somitogenesis and is dependent on BMP and etv2 signalling
Samuel J Capon, Kelly A Smith

Pluripotent Stem Cell-derived Cerebral Organoids Reveal Human Oligodendrogenesis with Dorsal and Ventral Origins
Hyosung Kim, Ranjie Xu, Padmashri Ragunathan, Anna Dunaevsky, Ying Liu, Cheryl F. Dreyfus, Peng Jiang

Neural tube development depends on notochord-derived Sonic hedgehog released into the sclerotome
Nitza Kahane, Chaya Kalcheim

Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization
Steven Hill, Andrew S. Blaeser, Austin A. Coley, Yajun Xie, Katherine A. Shepard, Corey C. Harwell, Wen-Jun Gao, A. Denise R. Garcia

A new role for Notch in control of polarity and asymmetric cell division of developing T cells
Mirren Charnley, Mandy Ludford-Menting, Kim Pham, Sarah M. Russell

The Clathrin adaptor AP-1 and the Rab-stabilizing chaperone Stratum act in two parallel pathways to control the activation of the Notch pathway in Drosophila
Karen Bellec, Isabelle Gicquel, Roland Le Borgne

Enhancer priming enables fast and sustained transcriptional responses to Notch signaling
Julia Falo-Sanjuan, Nicholas C Lammers, Hernan G Garcia, Sarah Bray

Programmed Switch in The Mitochondrial Degradation Pathways During Human Retinal Ganglion Cell Differentiation from Stem Cells is Critical for RGC Survival
Arupratan Das, Claire M. Bell, Cynthia A. Berlinicke, Nicholas Marsh-Armstrong, Donald J. Zack

Androgens enhance adult hippocampal neurogenesis in males but not females in an age-dependent manner
Paula Duarte-Guterman, Dwayne K. Hamson, Stephanie Lieblich, Steven R. Wainwright, Carmen Chow, Jessica Chaiton, Neil V. Watson, Liisa A.M. Galea

Dentate gyrus neurons that are born at the peak of development, but not before or after, die in adulthood
Tina Ciric, Shaina P. Cahill, Jason S. Snyder

Brain-synthesized estrogens regulate cortical migration in a sexually divergent manner
Katherine J. Sellers, Matthew C.S. Denley, Atsushi Saito, Atsushi Kamiya, Deepak P. Srivastava

The roles of Amh in zebrafish gonad development and sex determination
Yi-Lin Yan, Peter Batzel, Tom Titus, Jason Sydes, Thomas Desvignes, Ruth Bremiller, Bruce Draper, John H. Postlethwait

Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits
Daniele Linaro, Ben Vermaercke, Ryohei Iwata, Arjun Ramaswamy, Brittany A. Davis, Leila Boubakar, Baptiste Libé-Philippot, Angéline Bilheu, Lore De Bruyne, David Gall, Klaus Conzelmann, Vincent Bonin, Pierre Vanderhaeghen

Cortical Foxp2 supports behavioral flexibility and developmental dopamine D1 receptor expression
Marissa Co, Stephanie L. Hickey, Ashwinikumar Kulkarni, Matthew Harper, Genevieve Konopka

Expression of genes in the 16p11.2 locus during human fetal cortical neurogenesis
Sarah Morson, Yifei Yang, David J. Price, Thomas Pratt

Differential coupling of adult-born granule cells to parvalbumin and somatostatin interneurons
Ayelén I. Groisman, Sung M. Yang, Alejandro F. Schinder

Developmental changes in connectivity between the amygdala subnuclei and occipitotemporal cortex
Heather A. Hansen, Zeynep M. Saygin

Adult neurogenesis promotes efficient, nonspecific search strategies in a spatial alternation water maze task
Ru Qi Yu, Matthew Cooke, Jiaying Zhao, Jason S. Snyder

Emergence of consistent intra-individual locomotor patterns during zebrafish development
Jennifer A. Fitzgerald, Krishna T. Kirla, Carl P. Zinner, Colette M. vom Berg

STK11 is required for the normal program of ciliated cell differentiation in airways
Qiqi Chu, Changfu Yao, Xiangbing Qi, Barry Raymond Stripp, Nan Tang

| Morphogenesis & mechanics

Electric-induced reversal of morphogenesis in Hydra
Erez Braun, Hillel Ori

Neurogenin regulates effectors of migratory neuron cell behaviors in Ciona
Susanne Gibbonney, Kwantae Kim, Florian Razy-Krajka, Wei Wang, Alberto Stolfi

NEUROD2 represses Reelin expression and controls dendrite orientation during cortical radial migration
Gizem Guzelsoy, Cansu Akkaya, Dila Atak, Cory D. Dunn, Alkan Kabakcioglu, Nurhan Ozlu, Gulayse Ince-Dunn

Dynamic trafficking and turnover of Jam-C is essential for endothelial cell migration
Katja B. Kostelnik, Amy Barker, Christopher Schultz, Vinothini Rajeeve, Ian J. White, Michel Aurrand-Lions, Sussan Nourshargh, Pedro Cutillas, Thomas D. Nightingale

Knocking out non-muscle myosin II in retinal ganglion cells promotes long-distance optic nerve regeneration
Xue-Wei Wang, Shu-Guang Yang, Chi Zhang, Jin-Jin Ma, Yingchi Zhang, Bin-Bin Yang, Yi-Lan Weng, Guo-Li Ming, Anish R. Kosanam, Saijilafu, Feng-Quan Zhou

Actin assembly and non-muscle myosin activity drive dendrite retraction in an UNC-6/Netrin dependent self-avoidance response
Lakshmi Sundararajan, Cody J. Smith, Joseph D. Watson, Bryan A. Millis, Matthew J. Tyska, David M. Miller III

Integrins control tissue morphogenesis and homeostasis by sustaining the different types of intracellular actin networks
Carmen Santa-Cruz Mateos, Andrea Valencia-Expósito, David G. Míguez, Isabel M. Palacios, María D. Martín-Bermudo

Dual Role of Jam3b in Early Hematopoietic and Vascular Development
Isao Kobayashi, Jingjing Kobayashi-Sun, Yuto Hirakawa, Madoka Ouchi, Koyuki Yasuda, Hiroyasu Kamei, Shigetomo Fukuhara, Masaaki Yamaguchi

The Crk adapter protein is essential for Drosophila embryogenesis, where it regulates multiple actin-dependent morphogenic events
Andrew J. Spracklen, Emma M. Thornton-Kolbe, Alison N. Bonner, Alexandru Florea, Peter J. Compton, Rodrigo Fernandez-Gonzalez, Mark Peifer

Scribble and Discs-large direct adherens junction positioning and supermolecular assembly to establish apical-basal polarity
Teresa T. Bonello, Mark Peifer

Regulated spindle orientation buffers tissue growth in the epidermis
Angel Morrow, Julie Underwood, Lindsey Seldin, Taylor Hinnant, Terry Lechler

Two dynamical behaviours of the microtubules at cell cortex reveal pulling and pushing forces that position the spindle in C. elegans embryo
H. Bouvrais, L. Chesneau, D. Fairbrass, Y. Le Cunff, N. Soler, T. Pécot, C. Kervrann, J. Pécréaux

Membrane-type 1 matrix metalloproteinase (MMP-14) modulates tissue homeostasis by a non-proteolytic mechanism
Mukundan Attur, Cuijie Lu, Xiaodong Zhang, Cassidy Alexandre, Cristina Valacca, Shuai Zheng, Sarina Meikle, Branka Brukner Dabovic, Evelyne Tassone, Qing Yang, Victoria Kolupaeva, Shoshana Yakar, Steven Abramson, Paolo Mignatti

Mechanosensitive junction remodelling promotes robust epithelial morphogenesis
Michael F. Staddon, Kate E. Cavanaugh, Edwin M. Munro, Margaret L. Gardel, Shiladitya Banerjee

Microtubules promote intercellular contractile force transmission during tissue folding
Clint S. Ko, Vardges Tserunyan, Adam C. Martin

Transcriptional induction and mechanical propagation of a morphogenetic wave
Anais Bailles, Claudio Collinet, Jean-Marc Philippe, Pierre-François Lenne, Edwin Munro, Thomas Lecuit

| Genes & genomes

A Hox code defines spinocerebellar neuron subtype regionalisation
Eamon Coughlan, Victoria Garside, Siew Fen Lisa Wong, Huazheng Liang, Dominik Kraus, Kajari Karmakar, Upasana Maheshwari, Filippo M. Rijli, James Bourne, Edwina McGlinn

Nup93 modulates spatiotemporal dynamics and function of the HOXA gene cluster during differentiation
Ajay S Labade, Adwait Salvi, Krishanpal Karmodiya, Kundan Sengupta

A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life
Weidong Feng, Yinan Li, Pauline Dao, Jihad Aburas, Priota Islam, Benayahu Elbaz, Anna Kolarzyk, André E.X. Brown, Paschalis Kratsios

Nubp2 is required for cranial neural crest survival in the mouse
Andrew DiStasio, David Paulding, Praneet Chatuverdi, Rolf W. Stottmann

Atoh8 acts as a regulator of chondrocyte proliferation and differentiation in endochondral bones
Nadine Schroeder, Manuela Wuelling, Daniel Hoffmann, Beate Brand-Saberi, Andrea Vortkamp

Let-7 miRNAs control auditory sensory progenitor behavior in the vertebrate inner ear
Lale Evsen, Shuran Zhang, Angelika Doetzlhofer

The Polycomb group protein Ring1 regulates dorsoventral patterning of the mouse telencephalon
Hikaru Eto, Yusuke Kishi, Haruhiko Koseki, Yukiko Gotoh

EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells
R Ragazzini, R Pérez-Palacios, HI Baymaz, S Diop, K Ancelin, D Zielinski, A Michaud, M Givelet, M Borsos, S Aflaki, P Legoix, PWTC Jansen, N Servant, ME Torres-Padilla, D Bourc’his, P Fouchet, M Vermeulen, R Margueron

The Prrx1 limb enhancer marks an adult population of injury-responsive dermal fibroblasts
Joshua D. Currie, Lidia Grosser, Prayag Murawala, Maritta Schuez, Martin Michel, Elly M. Tanaka, Tatiana Sandoval-Guzmán

Precise removal of Calm1 long 3′ UTR isoform by CRISPR-Cas9 genome editing impairs dorsal root ganglion development in mice
Hannah N. Gruner, Bongmin Bae, Maebh Lynch, Daniel Oliver, Kevin So, Grant S. Mastick, Wei Yan, Pedro Miura

DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions
Matt J. Barter, Catherine Bui, Kathleen Cheung, Rodolfo Gómez, Andrew J. Skelton, Hannah R. Elliott, Louise N. Reynard, David A. Young

CTCF controls imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains by modulating allele-specific sub-TAD structure
David Llères, Benoît Moindrot, Rakesh Pathak, Vincent Piras, Mélody Matelot, Benoît Pignard, Alice Marchand, Mallory Poncelet, Aurélien Perrin, Virgile Tellier, Robert Feil, Daan Noordermeer

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation
Máté Pálfy, Gunnar Schulze, Eivind Valen, Nadine L. Vastenhouw

Improved single-cell ATAC-seq reveals chromatin dynamics of in vitro corticogenesis
Ryan M. Mulqueen, Brooke A. DeRosa, Casey A. Thornton, Zeynep Sayar, Kristof A. Torkenczy, Andrew J. Fields, Kevin M. Wright, Xiaolin Nan, Ramesh Ramji, Frank J. Steemers, Brian J. O’Roak, Andrew C. Adey

Differential chromatin accessibility in developing projection neurons is correlated with transcriptional regulation of cell fate
Whitney E. Heavner, Shaoyi Ji, James H. Notwell, Ethan S. Dyer, Alex M. Tseng, Johannes Birgmeier, Boyoung Yoo, Gill Bejerano, Susan K. McConnell

Single-cell chromatin accessibility analysis of mammary gland development reveals cell state transcriptional regulators and cellular lineage relationships
Chi-Yeh Chung, Zhibo Ma, Christopher Dravis, Sebastian Preissl, Olivier Poirion, Gidsela Luna, Xiaomeng Hou, Rajshekhar R. Giraddi, Bing Ren, Geoffrey M. Wahl

Unique Transcription Factor Functions Regulate Epigenetic and Transcriptional Dynamics During Cardiac Reprogramming
Nicole R. Stone, Casey A. Gifford, Reuben Thomas, Karishma J. B. Pratt, Kaitlen Samse-Knapp, Tamer M. A. Mohamed, Ethan M. Radzinsky, Amelia Schricker, Pengzhi Yu, Kathryn N. Ivey, Katherine S. Pollard, Deepak Srivastava

Resolving the 3D landscape of transcription-linked mammalian chromatin folding
Tsung-Han S. Hsieh, Elena Slobodyanyuk, Anders S. Hansen, Claudia Cattoglio, Oliver J. Rando, Robert Tjian, Xavier Darzacq

Detailed profiles of histone modification in male germ line cells of the young and aged mice
Misako Tatehana, Ryuichi Kimura, Kentaro Mochizuki, Noriko Osumi

Genome-wide 5-hydroxymethylcytosine (5hmC) emerges at early stage of in vitro hepatocyte differentiation
Jesús Rafael Rodríguez-Aguilera, Szilvia Ecsedi, Marie-Pierre Cros, Chloe Goldsmith, Mariana Domínguez-López, Nuria Guerrero-Celis, Rebeca Pérez-Cabeza de Vaca, Isabelle Chemin, Félix Recillas-Targa, Victoria Chagoya de Sánchez, Héctor Hernández-Vargas

Cell-type-specific genomics reveals histone modification dynamics in mammalian meiosis
Kwan-Wood Gabriel Lam, Kevin Brick, Gang Cheng, Florencia Pratto, R. Daniel Camerini-Otero

Single-cell transcriptional diversity is a hallmark of developmental potential
Gunsagar S. Gulati, Shaheen S. Sikandar, Daniel J. Wesche, Anoop Manjunath, Anjan Bharadwaj, Mark J. Berger, Francisco Ilagan, Angera H. Kuo, Robert W. Hsieh, Shang Cai, Maider Zabala, Ferenc A. Scheeren, Neethan A. Lobo, Dalong Qian, Feiqiao B. Yu, Frederick M. Dirbas, Michael F. Clarke, Aaron M. Newman

A Human Liver Cell Atlas: Revealing Cell Type Heterogeneity and Adult Liver Progenitors by Single-Cell RNA-sequencing
Nadim Aizarani, Antonio Saviano, Sagar, Laurent Mailly, Sarah Durand, Patrick Pessaux, Thomas F. Baumert, Dominic Grün

Decoding the development of the blood and immune systems during human fetal liver haematopoiesis
Dorin-Mirel Popescu, Rachel A Botting, Emily Stephenson, Kile Green, Laura Jardine, Emily F Calderbank, Mirjana Efremova, Meghan Acres, Daniel Maunder, Peter Vegh, Issac Goh, Yorick Gitton, Jongeun Park, Krzysztof Polanski, Roser Vento-Tormo, Zhichao Miao, Rachel Rowell, David McDonald, James Fletcher, David Dixon, Elizabeth Poyner, Gary Reynolds, Michael Mather, Corina Moldovan, Lira Mamanova, Frankie Greig, Matthew D Young, Kerstin Meyer, Steven Lisgo, Jaume Bacardit, Andrew Fuller, Ben Millar, Barbara Innes, Susan Lindsay, Michael J.T. Stubbington, Monika D Kowalczyk, Bo D Li, Orr Ashenbrg, Marcin D Tabaka, Danielle Dionne, Timothy L. Tickle, Michal Slyper, Orit Rozenblatt-Rosen, Andrew Filby, Alexandra-Chloe Villani, Anindita Roy, Aviv D Regev, Alain Chedotal, Irene Roberts, Berthold D Gottgens, Elisa Laurenti, Sam Behjati, Sarah D Teichmann, Muzlifah Haniffa

The Firre locus produces a trans-acting RNA molecule that functions in hematopoiesis
Jordan P. Lewandowski, James C. Lee, Taeyoung Hwang, Hongjae Sunwoo, Jill M. Goldstein, Abigail F. Groff, Nydia Chang, William Mallard, Adam Williams, Jorge Henao-Meija, Richard A. Flavell, Jeannie T. Lee, Chiara Gerhardinger, Amy J. Wagers, John L. Rinn

Insights about variation in meiosis from 31,228 human sperm genomes
Avery Davis Bell, Curtis J. Mello, James Nemesh, Sara A. Brumbaugh, Alec Wysoker, Steven A. McCarroll

The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing
Tianyanxin Sun, Tania L. Gonzalez, Nan Deng, Rosemarie DiPentino, Ekaterina L. Clark, Bora Lee, Jie Tang, Yizhou Wang, Barry R. Stripp, Changfu Yao, Hsian-Rong Tseng, S. Ananth Karumanchi, Alexander F. Koeppel, Stephen D. Turner, Charles R. Farber, Stephen S. Rich, Erica T. Wang, John Williams III, Margareta D. Pisarska

Single-cell analysis of Non-CG methylation dynamics and gene expression in human oocyte maturation
Bo Yu, Naresh Doni Jayavelu, Stephanie L. Battle, Thomas H. Smith, Samuel E Zimmerman, Timothy Schimmel, Jacques Cohen, Jessica C. Mar, R. David Hawkins

A cellular atlas of the developing meninges reveals meningeal fibroblast diversity and function
John DeSisto, Rebecca O’Rourke, Stephanie Bonney, Hannah E. Jones, Fabien Guimiot, Kenneth L. Jones, Julie A. Siegenthaler

Placental effects on maternal brain revealed by disrupted placental gene expression in mouse hybrids
Lena Arévalo, Polly Campbell

Screening human embryos for polygenic traits has limited utility
Ehud Karavani, Or Zuk, Danny Zeevi, Gil Atzmon, Nir Barzilai, Nikos C. Stefanis, Alex Hatzimanolis, Nikolaos Smyrnis, Dimitrios Avramopoulos, Leonid Kruglyak, Max Lam, Todd Lencz, Shai Carmi

Contribution of Retrotransposition to Developmental Disorders
Eugene J. Gardner, Elena Prigmore, Giuseppe Gallone, Petr Danecek, Kaitlin E. Samocha, Juliet Handsaker, Sebastian S. Gerety, Holly Ironfield, Patrick J. Short, Alejandro Sifrim, Tarjinder Singh, Kate E. Chandler, Emma Clement, Katherine L. Lachlan, Katrina Prescott, Elisabeth Rosser, David R. FitzPatrick, Helen V. Firth, Matthew E. Hurles, on behalf of the Deciphering Developmental Disorders study

AP-1 Imprints a Reversible Transcriptional Program of Senescent Cells
Ricardo Iván Martínez-Zamudio, Pierre-François Roux, José Américo N L F de Freitas, Lucas Robinson, Gregory Doré, Bin Sun, Jesús Gil, Utz Herbig, Oliver Bischof

Single-cell transcriptomes of the aging human skin reveal loss of fibroblast priming
Llorenç Solé-Boldo, Günter Raddatz, Sabrina Schütz, Jan-Philipp Mallm, Karsten Rippe, Anke S. Lonsdorf, Manuel Rodríguez-Paredes, Frank Lyko

Identification of master regulators in goblet cells and Paneth cells using transcriptomics profiling of gut organoids and multi-layered networks
A Treveil, P Sudhakar, Z J Matthews, T Wrzesinski, E J Jones, J Brooks, M Olbei, I Hautefort, L J Hall, S R Carding, U Mayer, P P Powell, T Wileman, F Di Palma, W Haerty, T Korcsmáros

Comparative analysis of diverse cell states establishes an epigenetic basis for inferring regulatory genes governing cell identity
Woo Jun Shim, Enakshi Sinniah, Jun Xu, Burcu Vitrinel, Michael Alexanian, Gaia Andreoletti, Sophie Shen, Brad Balderson, Guangdun Peng, Naihe Jing, Yuliangzi Sun, Yash Chhabra, Yuliang Wang, Patrick P L Tam, Aaron Smith, Michael Piper, Lionel Christiaen, Quan Nguyen, Mikael Bodén, Nathan J. Palpant

A conserved regulatory program drives emergence of the lateral plate mesoderm
Karin D. Prummel, Christopher Hess, Susan Nieuwenhuize, Hugo J. Parker, Katherine W. Rogers, Iryna Kozmikova, Claudia Racioppi, Eline C. Brombacher, Anna Czarkwiani, Dunja Knapp, Sibylle Burger, Elena Chiavacci, Gopi Shah, Alexa Burger, Jan Huisken, Maximina H. Yun, Lionel Christiaen, Zbynek Kozmik, Patrick Müller, Marianne Bronner, Robb Krumlauf, Christian Mosimann

Transgenerational inheritance of betaine-induced epigenetic alterations in estrogen-responsive IGF-2/IGFBP2 genes in rat hippocampus
Yang Yang, Shu Yang, Wenduo Jiang, Fulei Qi, Ruqian Zhao

Somatic cell nuclear transfer in non-enucleated goldfish oocytes: understanding DNA fate during meiosis resumption and first cellular division
Charlène Rouillon, Alexandra Depincé, Nathalie Chênais, Pierre-Yves Le Bail, Catherine Labbé

Dose-dependent functions of SWI/SNF BAF in permitting and inhibiting cell proliferation in vivo
Aniek van der Vaart, Molly Godfrey, Vincent Portegijs, Sander van den Heuvel

A Pandas complex adapted for piRNA-guided transposon silencing
Kang Zhao, Sha Cheng, Na Miao, Ping Xu, Xiaohua Lu, Ming Wang, Yuhan Zhang, Xun Yuan, Weiwei Liu, Xin Lu, Xuan Ouyang, Peng Zhou, Jiaqi Gu, Yiqun Zhang, Ding Qiu, Shan Wang, Zhaohui Jin, Youzhong Wan, Jinbiao Ma, Hong Cheng, Ying Huang, Yang Yu

Evidence that Runt Acts as a Counter-Repressor of Groucho during Drosophila melanogaster Primary Sex Determination
Sharvani Mahadeveraju, James W. Erickson

| Stem cells, regeneration & disease modelling

Cell cycle regulators control mesoderm specification in human pluripotent stem cells
Loukia Yiangou, Rodrigo A. Grandy, Sanjay Sinha, Ludovic Vallier

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression
Anna SE Cuomo, Daniel D Seaton, Davis J McCarthy, Iker Martinez, Marc Jan Bonder, Jose Garcia-Bernardo, Shradha Amatya, Pedro Madrigal, Abigail Isaacson, Florian Buettner, Andrew Knights, Kedar Nath Natarajan, HipSci Consortium, Ludovic Vallier, John C Marioni, Mariya Chhatriwala, Oliver Stegle

Human iPSC gene signatures and X chromosome dosage impact response to WNT inhibition and cardiac differentiation fate
Agnieszka D’Antonio-Chronowska, Margaret K. R. Donovan, Paola Benaglio, William W. Greenwald, Michelle C. Ward, Hiroko Matsui, Kyohei Fujita, Sherin Hashem, Francesca Soncin, Mana Parast, Eric Adler, Erin N. Smith, Matteo D’Antonio, Kelly A. Frazer

Analysis of the expression of PIWI-interacting RNAs during cardiac differentiation of human pluripotent stem cells
Alejandro La Greca, María Agustina Scarafía, María Clara Hernández Cañás, Nelba Pérez, Sheila Castañeda, Carolina Colli, Alan Miqueas Möbbs, Natalia Lucía Santín Velazque, Gabriel Neiman, Ximena Garate, Cyntia Aban, Ariel Waisman, Lucía Moro, Gustavo Sevlever, Carlos Luzzani, Santiago Miriuka

Intestinal stem cell differentiation is associated with dynamic changes in the chromatin landscape
Jesse R Raab, Kortney E Wager, Jeremy M Morowitz, Scott T Magness, Adam D Gracz

Endogenous fluctuations of OCT4 and SOX2 bias pluripotent cell fate decisions
Daniel Strebinger, Cédric Deluz, Elias T. Friman, Subashika Govindan, Andrea B. Alber, David M. Suter

Efficient RNA-mediated reprogramming of human somatic cells to naïve pluripotency facilitated by tankyrase inhibition
Nicholas Bredenkamp, Jian Yang, James Clarke, Giuliano Giuseppe Stirparo, Ferdinand von Meyenn, Duncan Baker, Rosalind Drummond, Dongwei li, Chuman Wu, Maria Rostovskaya, Austin Smith, Ge Guo

KLF4 protein stability regulated by interaction with pluripotency transcription factors overrides transcriptional control
Navroop K Dhaliwal, Luis E Abatti, Jennifer A Mitchell

Context-dependent requirement of H3K9 methyltransferase activity during cellular reprogramming to iPSCs
Simon Vidal, Alexander Polyzos, Jorge Morales Valencia, Hongsu Wang, Emily Swanzey, Ly-sha Ee, Bhishma Amlani, Shengjiang Tu, Yixiao Gong, Aristotelis Tsirigos, Sangyong Kim, Effie Apostolou, Matthias Stadtfeld

Nonreciprocal and Conditional Cooperativity Directs the Pioneer Activity of Pluripotency Transcription Factors
Sai Li, Eric Bo Zheng, Li Zhao, Shixin Liu

High-throughput propagation of human prostate tissue from induced-pluripotent stem cells
AC Hepburn, EL Curry, M Moad, RE Steele, OE Franco, L Wilson, P Singh, SE Crawford, Luke Gaughan, IG Mills, SW Hayward, CN Robson, R Heer

GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocytes
Peter R.T. Bowman, Godfrey L Smith, Gwyn W Gould

Assessment of the in vitro function of human stem cell-derived β cells
Arvind R. Srivatsava, Stefanie T. Shahan, Lisa C. Gutgesell, Leonardo Velazco-Cruz, Jeffrey R. Millman

Hydrogel platform for in vitro three-dimensional assembly of human stem cell-derived β cells and endothelial cells
Punn Augsornworawat, Leonardo Velazco-Cruz, Jiwon Song, Jeffrey R. Millman

Cross-species blastocyst chimerism between nonhuman primates using iPSCs
Morteza Roodgar, Fabian P. Suchy, Vivek Bajpai, Jose G. Viches-Moure, Joydeep Bhadury, Angelos Oikonomopoulos, Joseph C. Wu, Joseph L. Mankowski, Kyle M. Loh, Hiromitsu Nakauchi, Catherine VandeVoort, Michael P. Snyder

Spatial genome re-organization between fetal and adult hematopoietic stem cells
C Chen, W Yu, J Tober, P Gao, B He, K Lee, T Trieu, GA Blobel, NA Speck, K Tan

Changes in the expression of mitochondrial morphology-related genes during the differentiation of murine embryonic stem cells
Jeong Eon Lee, Bong Jong Seo, Min Ji Han, Yean Ju Hong, Kwonho Hong, Hyuk Song, Jeong Woong Lee, Jeong Tae Do

Stirred Suspension Bioreactor Culture of Porcine Induced Pluripotent Stem Cells
Kyle Burrell, Rkia Dardari, Taylor Goldsmith, Derek Toms, Daniel A.F. Villagomez, W. Allan King, Mark Ungrin, Franklin D. West, Ina Dobrinski

Shavenbaby protein isoforms orchestrate the self-renewal versus differentiation of Drosophila intestinal stem cells
Sandy Al Hayek, Ahmad Alsawadi, Zakaria Kambris, Jean-Philippe Boquete, Jérôme Bohère, Brice Ronsin, Serge Plaza, Bruno Lemaitre, François Payre, Dani Osman

CENP-A drives asymmetric cell division and maintains stem identity
Anna A. Dattoli, Ben L. Carty, Antje M. Kochendoerfer, Annie E. Walshe, Elaine M. Dunleavy

A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine
Jakob von Frieling, Muhammed Naeem Faisal, Femke Sporn, Roxana Pfefferkorn, Stella Solveig Nolte, Felix Sommer, Philip Rosenstiel, Thomas Roeder

Quantification of the morphological characteristics of hESC colonies
Sirio Orozco-Fuentes, Irina Neganova, Laura E. Wadkin, Andrew W. Baggaley, Rafael A. Barrio, Majlinda Lako, Anvar Shukurov, Nicholas G. Parker

Primordial Blasts, a population of blood borne stem cells responsible for whole body regeneration in a basal chordate
Susannah H Kassmer, Adam D Langenbacher, Anthony W De Tomaso

Taurine promotes axonal regeneration after a complete spinal cord injury in lampreys
Daniel Sobrido-Cameán, Blanca Fernández-López, Natividad Pereiro, Anunciación Lafuente, María Celina Rodicio, Antón Barreiro-Iglesias

Tissue Engineered Axon Tracts Serve as Living Scaffolds to Accelerate Axonal Regeneration and Functional Recovery Following Peripheral Nerve Injury in Rats
Kritika S. Katiyar, Laura A. Struzyna, Joseph P. Morand, Justin C. Burrell, Basak Clements, Franco A. Laimo, Kevin D. Browne, Joachim Kohn, Zarina Ali, Harry C. Ledebur, Douglas H. Smith, D. Kacy Cullen

Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse
Feini Qu, Ilan C. Palte, Paul M. Gontarz, Bo Zhang, Farshid Guilak

Regulation of CNS regeneration-associated genes is driven by a temporally changing cast of transcription factors
Sumona P. Dhara, Andrea Rau, Michael J. Flister, Nicole M. Recka, Michael D. Laiosa, Paul L. Auer, Ava J. Udvadia

Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish
Nicholas J. Silva, Mikiko Nagashima, Jingling Li, Laura Kakuk-Atkins, Milad Ashrafzadeh, David R. Hyde, Peter F. Hitchcock

Understanding the basis of CYP26 mediated regulation of lens regeneration using ex vivo eye cultures and 4-oxo-RA
Alvin G Thomas, Mohd Tayyab Adil, Jonathan J Henry

Skeletal muscle stem cell self-renewal and differentiation kinetics revealed by EdU lineage tracing during regeneration
Bradley Pawlikowski, Nicole Dalla Betta, Tiffany Antwine, Bradley B. Olwin

A cellular atlas of skeletal muscle regeneration and aging
Bradley Pawlikowski, Nicole Dalla Betta, Tiffany Elston, Rebecca O’Rourke, Kenneth Jones, Bradley B. Olwin

Gene editing preserves visual function in a mouse model of retinal degeneration
Paola Vagni, Laura E. Perlini, Naïg A. L. Chenais, Tommaso Marchetti, Martina Parrini, Andrea Contestabile, Laura Cancedda, Diego Ghezzi

Novel mouse model of encephalocele: post-neurulation origin and relationship to open neural tube defects
Ana Rolo, Gabriel L. Galea, Dawn Savery, Nicholas D. E. Greene, Andrew J. Copp

Imprinting effects of UBE3A loss on synaptic gene networks and Wnt signaling pathways
S. Jesse Lopez, Benjamin I. Laufer, Ulrika Beitnere, Elizabeth L. Berg, Jill L. Silverman, David J. Segal, Janine M. LaSalle

Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons
Emily M.A. Lewis, Kesavan Meganathan, Dustin Baldridge, Paul Gontarz, Bo Zhang, Azad Bonni, John N. Constantino, Kristen L. Kroll

OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome
Ranjie Xu, Andrew T Brawner, Shenglan Li, JingJing Liu, Hyosung Kim, Haipeng Xue, Zhiping P. Pang, Woo-Yang Kim, Ronald P. Hart, Ying Liu, Peng Jiang

SF3B1 cancer-related mutations cause vulnerability to further perturbations in the U2 snRNP complex in C. elegans
Xènia Serrat, Dmytro Kukhtar, Eric Cornes, Anna Esteve-Codina, Helena Benlloch, Germano Cecere, Julián Cerón

Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics
Teresa G Krieger, Stephan M Tirier, Jeongbin Park, Tanja Eisemann, Heike Peterziel, Peter Angel, Roland Eils, Christian Conrad

Targetable cellular signaling events drive arterial rupture in knock-in mouse models of vascular Ehlers-Danlos Syndrome
Caitlin J. Bowen, Juan Francisco Calderón Giadrosic, Graham Rykiel, Zachary Burger, Elaine C. Davis, Mark R. Helmers, Elena Gallo MacFarlane, Harry C. Dietz

Huntington phosphorylation governs BDNF homeostasis and improves the phenotype of Mecp2 knockout mice
Yann Ehinger, Julie Bruyère, Nicolas Panayotis, Yah-Se Abada, Lydia Saidi, Valérie Matagne, Chiara Scaramuzzino, Hélène Vitet, Benoit Delatour, Laurent Villard, Frédéric Saudou, Jean-Christophe Roux

| Plant development

Distinct RopGEFs successively drive polarization and outgrowth of root hairs
Philipp Denninger, Anna Reichelt, Vanessa A. F. Schmidt, Dietmar G. Mehlhorn, Lisa Y. Asseck, Claire E. Stanley, Nana F. Keinath, Jan-Felix Evers, Christopher Grefen, Guido Grossmann

PICKLE recruits RETINOBLASTOMA RELATED 1 to Control Lateral Root Formation in Arabidopsis
Krisztina Ötvös, Pál MIskolczi, Peter Marhavý, Alfredo Cruz-Ramírez, Eva Benková, Stéphanie Robert, László Bakó

The cap size and shape of Arabidopsis thaliana primary roots impact the root responses to an increase in medium strength
J. Roué, H. Chauvet, N. Brunel-Michac, F. Bizet, B. Moulia, E. Badel, V. Legué

Root development is maintained by specific bacteria-bacteria interactions within a complex microbiome
Omri M. Finkel, Isai Salas-González, Gabriel Castrillo, Theresa F. Law, Jonathan M. Conway, Corbin D. Jones, Jeffery L. Dangl

MLKS2 is an ARM domain and F-actin-associated KASH protein that functions in stomatal complex development and meiotic chromosome segregation
Hardeep K. Gumber, Joseph F. McKenna, Andrea F. Tolmie, Alexis M. Jalovec, Andre C. Kartick, Katja Graumann, Hank W. Bass

Unfolded protein-independent IRE1 activation contributes to multifaceted developmental processes in Arabidopsis
Kei-ichiro Mishiba, Yuji Iwata, Tomofumi Mochizuki, Atsushi Matsumura, Nanami Nishioka, Rikako Hirata, Nozomu Koizumi

BIOTIN ATTACHMENT DOMAIN-CONTAINING proteins, inhibitors of ACCase, are regulated by WRINKLED1
Hui Liu, Zhiyang Zhai, Kate Kuczynski, Jantana Keereetaweep, Jorg Schwender, John Shanklin

Brassinosteroid signaling controls PILS-dependent nuclear auxin input in Arabidopsis thaliana
Lin Sun, Elena Feraru, Mugurel I. Feraru, Jürgen Kleine-Vehn

Auxin-Induced Actin Cytoskeleton Rearrangements Require AUX1
Ruthie S. Arieti, Christopher J. Staiger

ARGONAUTE5 Mediates Fine-Tuning of Vegetative-to-Reproductive Phase Transition Through Its Interaction with miR156 in Arabidopsis
Charles Roussin-Léveillée, Guilherme Silva-Martins, Peter Moffett

miRNA-encoded peptide, miPEP858, regulates plant growth and development in Arabidopsis
Ashish Sharma, Poorwa Kamal Badola, Chitra Bhatia, Deepika Sharma, Prabodh Kumar Trivedi

MicroRNA Dynamics and Functions During Arabidopsis Embryogenesis
Alexandra Plotnikova, Max J. Kellner, Magdalena Mosiolek, Michael A. Schon, Michael D. Nodine

The Catalytic Core of DEMETER Guides Active DNA Demethylation in Arabidopsis
Changqing Zhang, Yu-Hung Hung, Xiang-Qian Zhang, Dapeng Zhang, Jennifer M. Frost, Fang Liu, Wenyan Xiao, Lakshminarayan M. Iyer, L. Aravind, Jin Hoe Huh, Robert L. Fischer, Tzung-Fu Hsieh

Chloroplast nucleoids are highly dynamic in ploidy, number, and structure during leaf development
Stephan Greiner, Hieronim Golczyk, Irina Malinova, Tommaso Pellizzer, Ralph Bock, Thomas Börner, Reinhold G. Herrmann

Mechanical stress initiates and sustains the morphogenesis of wavy leaf epidermal cells
Amir J Bidhendi, Bara Altartouri, Frederick Gosselin, Anja Geitmann

Evolution of vascular plants through redeployment of ancient developmental regulators
Nicole van ’t Wout Hofland, Kuan-Ju Lu, Eliana Mor, Sumanth Mutte, Paul Abrahams, Hirotaka Kato, Klaas Vandepoele, Dolf Weijers, Bert De Rybel

Wheat VRN1, FUL2 and FUL3 play critical and redundant roles in spikelet development and spike determinacy
Chengxia Li, Huiqiong Lin, Andrew Chen, Meiyee Lau, Judy Jernstedt, Jorge Dubcovsky

Transcriptomic response to divergent selection for flowering time in maize reveals convergence and key players of the underlying gene regulatory network
Maud Irène Tenaillon, Khawla Sedikki, Maeva Mollion, Martine Le Guilloux, Elodie Marchadier, Adrienne Ressayre, Christine Dillmann

Changes in lipid composition and ultrastructure associated with functional maturation of the cuticle during adult maize leaf development
Richard Bourgault, Susanne Matschi, Miguel Vasquez, Pengfei Qiao, Annika Sonntag, Caleb Charlebois, Marc Mohammadi, Michael J. Scanlon, Laurie G. Smith, Isabel Molina

From bud formation to flowering: transcriptomic state defines the cherry developmental phases of sweet cherry bud dormancy
Noémie Vimont, Mathieu Fouché, José Antonio Campoy, Meixuezi Tong, Mustapha Arkoun, Jean-Claude Yvin, Philip A. Wigge, Elisabeth Dirlewanger, Sandra Cortijo, Bénédicte Wenden

The persimmon genome reveals clues to the evolution of a lineage-specific sex determination system in plants
Takashi Akagi, Kenta Shirasawa, Hideki Nagasaki, Hideki Hirakawa, Ryutaro Tao, Luca Comai, Isabelle M. Henry

Evo-devo & evo

Morphology and development of the Portuguese man of war, Physalia physalis
Catriona Munro, Zer Vue, Richard R. Behringer, Casey W. Dunn

Loss of developmental diapause as a prerequisite for social evolution in bees
Priscila Karla Ferreira Santos, Maria Cristina Arias, Karen M. Kapheim

An adult brain atlas reveals broad neuroanatomical changes in independently evolved populations of Mexican cavefish
Cody Loomis, Robert Peuß, James Jaggard, Yongfu Wang, Sean McKinney, Stephen Raftopoulos, Austin Raftopoulos, Daniel Whu, Matthew Green, Suzanne E. McGaugh, Nicolas Rohner, Alex C. Keene, Erik R. Duboue

Genomic analysis of the tryptome reveals molecular mechanisms of gland cell evolution
Leslie S. Babonis, Joseph F. Ryan, Camille Enjolras, Mark Q. Martindale

The evolutionary origins and diversity of the neuromuscular system of paired appendages in batoids
Natalie Turner, Deimante Mikalauskaite, Krista Barone, Kathleen Flaherty, Gayani Senevirathne, Noritaka Adachi, Neil H Shubin, Tetsuya Nakamura

Spatial cell disparity in the colonial choanoflagellate Salpingoeca rosetta
Benjamin Naumann, Pawel Burkhardt

Insulin-like growth factor 1 is related to the expression of plumage traits in a passerine species
Katharina Mahr, Orsolya Vincze, Zsófia Tóth, Herbert Hoi, Ádám Z. Z Lendvai

Multiple loci control eyespot number variation on the hindwings of Bicyclus anynana butterflies
Angel G. Rivera-Colón, Erica L. Westerman, Steven M. Van Belleghem, Antónia Monteiro, Riccardo Papa

Evolution of Larval Segment Position across 12 Drosophila Species
Gizem Kalay, Joel Atallah, Noemie C. Sierra, Austin M. Tang, Amanda E. Crofton, Mohan K. Murugesan, Sherri Wykoff-Clary, Susan E. Lott

Early origin and deep conservation of enhancers in animals
Emily S Wong, Siew Zhuan Tan, Victoria Garside, Gilles Vanwalleghem, Federico Gaiti, Ethan Scott, Edwina McGlinn, Mathias Francois, Bernard M Degnan

FGF signalling plays similar roles in development and regeneration of the skeleton in the brittle star Amphiura filiformis
Anna Czarkwiani, David V. Dylus, Luisana Carballo, Paola Oliveri

Neuron subtype-specific effector gene expression in the Motor Ganglion of Ciona
Susanne Gibboney, Kwantae Kim, Christopher J. Johnson, Jameson Orvis, Paula Martínez-Feduchi, Elijah K. Lowe, Sarthak Sharma, Alberto Stolfi

A nemertean excitatory peptide/CCHamide regulates ciliary swimming in the larvae of Lineus longissimus
Daniel Thiel, Philipp Bauknecht, Gáspár Jékely, Andreas Hejnol

Reciprocal requirement of Wnt signaling and SKN-1 underlies cryptic intraspecies variation in an ancient embryonic gene regulatory network
Yamila N. Torres Cleuren, Chee Kiang Ewe, Kyle C. Chipman, Emily Mears, Cricket G. Wood, Coco A.E. Al-Alami, Melissa R. Alcorn, Thomas L. Turner, Pradeep M. Joshi, Russell G. Snell, Joel H. Rothman

Methylation and Gene Expression Differences Between Reproductive Castes of Bumblebee Workers
Hollie Marshall, Zoë N. Lonsdale, Eamonn B. Mallon

Evolution of limb development in cephalopod mollusks
Oscar A. Tarazona, Davys H. Lopez, Leslie A. Slota, Martin J. Cohn

Differential sperm motility mediates the sex ratio drive shaping mouse sex chromosome evolution
CC Rathje, EEP Johnson, D Drage, C Patinioti, G Silvestri, NA Affara, C Ialy-Radio, J Cocquet, BM Skinner, PJI Ellis

Ecological scaffolding and the evolution of individuality: the transition from cells to multicellular life
Andrew J Black, Pierrick Bourrat, Paul B Rainey

DNA methylation facilitates local adaptation and adaptive transgenerational plasticity
Melanie J. Heckwolf, Britta S. Meyer, Robert Häsler, Marc P. Höppner, Christophe Eizaguirre, Thorsten B. H. Reusch

Cell biology

Intertwined Functions of Separase and Caspase in Cell Division and Programmed Cell Death
Pan-Young Jeong, Ashish Kumar, Pradeep Joshi, Joel H. Rothman

The C. elegans Tubby homolog dynamically modulates olfactory cilia membrane morphogenesis and phospholipid composition
Danielle DiTirro, Alison Philbrook, Kendrick Rubino, Piali Sengupta

Stochastic and coincident control of terminal cell differentiation and cell cycle exit
Michael L. Zhao, Kyle M. Kovary, Atefeh Rabiee, Zahra Bahrami-Nejad, Brooks Taylor, Mary N. Teruel

Identification of genes required for apical protein trafficking in Drosophila photoreceptor cells
Azadeh Laffafian, Ulrich Tepass

Combinatorial perturbation analysis reveals divergent regulations of mesenchymal genes during epithelial-to-mesenchymal transition
Kazuhide Watanabe, Nicholas Panchy, Shuhei Noguchi, Harukazu Suzuki, Tian Hong

Precise tuning of cortical contractility regulates cell shape during cytokinesis
Nilay Taneja, Matthew R. Bersi, Sophie Baillargeon, Aidan M. Fenix, James A. Cooper, Ryoma Ohi, Vivian Gama, W. David Merryman, Dylan T. Burnette

Actin chromobody imaging reveals sub-organellar actin dynamics
Cara Schiavon, Tong Zhang, Bing Zhao, Leonardo Andrade, Melissa Wu, Tsung-Chang Sung, Yelena Dayn, Jasmine W. Feng, Omar A. Quintero, Robert Grosse, Uri Manor

Ultrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings
Stéphane Vassilopoulos, Solène Gibaud, Angélique Jimenez, Ghislaine Caillol, Christophe Leterrier

SNAP23 is required for constitutive and regulated exocytosis in mouse oocytes
Lisa M. Mehlmann, Tracy F. Uliasz, Katie M. Lowther

Simultaneous regulation of cytokinetic furrow and nucleus positions by cortical tension contributes to proper DNA segregation during late mitosis
Anne Pacquelet, Matthieu Jousseaume, Jocelyn Etienne, Grégoire Michaux

Modelling

Constraints on somite formation in developing embryos
Jonas S. Juul, Mogens H. Jensen, Sandeep Krishna

Leader cells in collective chemotaxis: optimality and tradeoffs
Austin Hopkins, Brian A. Camley

Modeling cell migration regulated by cell-ECM micromechanical coupling
Yu Zheng, Hanqing Nan, Qihui Fan, Xiaochen Wang, Liyu Liu, Ruchuan Liu, Fangfu Ye, Bo Sun, Yang Jiao

A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms
Arnab Barua, Josue M. Nava-Sedeño, Haralampos Hatzikirou

Physical Models of Collective Cell Migration
Ricard Alert, Xavier Trepat

Modeling tissue growth with the Stokes equation
Teemu J Hakkinen, Jukka Jernvall, Antti Hannukainen

On early brain folding patterns using biomechanical growth modeling
Xiaoyu Wang, Amine Bohi, Mariam Al Harrach, Mickael Dinomais, Julien Lefèvre, François Rousseau

Surface tension controls the onset of gyrification in brain organoids
Davide Riccobelli, Giulia Bevilacqua

A VEGF reaction-diffusion mechanism that selects variable densities of endothelial tip cells
W. Bedell, A. D. Stroock

Plasticity of cell migration resulting from mechanochemical coupling
Yuansheng Cao, Elisabeth Ghabache, Wouter-Jan Rappel

A demographic model for estimating the inter-division lifespans of stem cells and the subsequent transit amplifying stages
Purna Gadre, Shambhabi Chatterjee, Bhavna Varshney, Debasmita Mazumdar, Samir Gupta, Nitin Nitsure, Krishanu Ray

Tools & resources

An optimized protocol for iDISCO+ rat brain clearing, imaging, and analysis
Audrey Branch, Daniel Tward, Joshua T Vogelstein, Zhuhao Wu, Michela Gallagher

Cellular and Molecular Probing of Intact Transparent Human Organs
Shan Zhao, Mihail Ivilinov Todorov, Ruiyao Cai, Hanno Steinke, Elisabeth Kemter, Eckhard Wolf, Jan Lipfert, Ingo Bechmann, Ali Ertürk

Automated cell boundary and 3D nuclear segmentation of cells in suspension
Benjamin Kesler, Guoliang Li, Alexander Thiemicke, Rohit Venkat, Gregor Neuert

Simultaneous 3D super-resolution fluorescence microscopy and atomic force microscopy: combined SIM and AFM platform for cell imaging
Ana I. Gomez-Varela, Dimitar R. Stamov, Adelaide Miranda, Rosana Alves, Claudia Barata-Antunes, Daphne Dambournet, David G. Drubin, Sandra Paiva, Pieter A. A. De Beule

A low-cost and high-precision scanning electrochemical microscope built with open source tools
Alperen Guver, Nafetalai Fifita, Peker Milas, Michael Straker, Michael Guy, Kara Green, Taha Yildirim, Ilyas Unlu, Veysel Yigit, Birol Ozturk

Quantifying Three-dimensional Chromatin Organization Utilizing Scanning Transmission Electron Microscopy: ChromSTEM
Yue Li, Eric Roth, Vasundhara Agrawal, Adam Eshein, Jane Fredrick, Luay Almassalha, Anne Shim, Reiner Bleher, Vinayak P. Dravid, Vadim Backman

Application of extracellular flux analysis for determining mitochondrial function in mammalian oocytes and early embryos
Bethany Muller, Niamh Lewis, Tope Adeniyi, Henry J Leese, Daniel Brison, Roger G Sturmey

Fast, Efficient, and Precise Gene Editing in the Moss Physcomitrella patens
Peishan Yi, Gohta Goshima

Proximity labeling of protein complexes and cell type-specific organellar proteomes in Arabidopsis enabled by TurboID
Andrea Mair, Shou-Ling Xu, Tess C. Branon, Alice Y. Ting, Dominique C. Bergmann

The Vertebrate Codex Gene Breaking Protein Trap Library For Genomic Discovery and Disease Modeling Applications
Noriko Ichino, MaKayla Serres, Rhianna Urban, Mark Urban, Kyle Schaefbauer, Lauren Greif, Gaurav K. Varshney, Kimberly J. Skuster, Melissa McNulty, Camden Daby, Ying Wang, Hsin-kai Liao, Suzan El-Rass, Yonghe Ding, Weibin Liu, Lisa A. Schimmenti, Sridhar Sivasubbu, Darius Balciunas, Matthias Hammerschmidt, Steven A. Farber, Xiao-Yan Wen, Xiaolei Xu, Maura McGrail, Jeffrey J. Essner, Shawn Burgess, Karl J. Clark, Stephen C. Ekker

Tmem119-EGFP and Tmem119-CreERT2 transgenic mice for labeling and manipulating microglia
Tobias Kaiser, Guoping Feng

Generation of transgenic quails by in vivo transfection of primordial germ cells
Olivier Serralbo, Nadège Véron, Caitlin Cooper, Marie-Julie Dejardin, Timothy Doran, Christophe Marcelle

Gene knock-ins in Drosophila using homology-independent insertion of universal donor plasmids
Justin A. Bosch, Ryan Colbeth, Jonathan Zirin, Norbert Perrimon

A large-scale resource for tissue-specific CRISPR mutagenesis in Drosophila
Fillip Port, Claudia Strein, Mona Stricker, Benedikt Rauscher, Florian Heigwer, Jun Zhou, Celine Beyersdörffer, Jana Frei, Amy Hess, Katharina Kern, Roberta Malamud, Bojana Pavlovic, Kristin Rädecke, Lukas Schmitt, Lukas Voos, Erica Valentini, Michael Boutros

Golden Mutagenesis: An efficient multi-sitesaturation mutagenesis approach by Golden Gate cloning with automated primer design
Pascal Püllmann, Chris Ulpinnis, Sylvestre Marillonnet, Ramona Gruetzner, Steffen Neumann, Martin J. Weissenborn

Expanding the crispr toolbox with mad7 in zebrafish and human cells
Wesley A. Wierson, Brandon W. Simone, Zachary WareJoncas, Carla Mann, Jordan M. Welker, William A. C. Gendron, Michael A. Barry, Karl J. Clark, Drena Dobbs, Maura McGrail, Stephen C. Ekker, Jeffrey J. Essner

Efficient strategies to detect genome editing and integrity in CRISPR-Cas9 engineered ESCs
Maja Gehre, Christopher Buccitelli, Nichole Diaz, Jan Korbel, Kyung-Min Noh

CRISPR adenine and cytosine base editors with reduced RNA off-target activities
Julian Grünewald, Ronghao Zhou, Sowmya Iyer, Caleb A. Lareau, Sara P. Garcia, Martin J. Aryee, J. Keith Joung

Tissue-specific Genome Editing in vivo by MicroRNA-repressible Anti-CRISPR Proteins
Jooyoung Lee, Haiwei Mou, Raed Ibraheim, Shun-Qing Liang, Wen Xue, Erik Sontheimer

CLADES: a programmable sequence of reporters for lineage analysis
Jorge Garcia-Marques, Ching-Po Yang, Isabel Espinosa-Medina, Minoru Koyama, Tzumin Lee

A Novel Chromatin-Opening Element for Stable Long-term Transgene Expression
Shireen S. Rudina, Christina D. Smolke

Quantifying the dynamics of hematopoiesis by in vivo IdU pulse-chase, mass cytometry and mathematical modeling
Amir Erez, Ratnadeep Mukherjee, Grégoire Altan-Bonnet

Improved CUT&RUN chromatin profiling and analysis tools
Michael P. Meers, Terri Bryson, Steven Henikoff

Proxies of CRISPR-Cas9 activity to aid in the identification of mutagenized Arabidopsis plants
Renyu Li, Charles Vavrik, Cristian H. Danna

3D RNA-seq – a powerful and flexible tool for rapid and accurate differential expression and alternative splicing analysis of RNA-seq data for biologists
Wenbin Guo, Nikoleta Tzioutziou, Gordon Stephen, Iain Milne, Cristiane Calixto, Robbie Waugh, John WS Brown, Runxuan Zhang

Production of interspecies somatic/pluripotent heterokaryons using polyethylene glycol (PEG) and selection by imaging flow cytometry for the study of nuclear reprogramming
M. Cristina Villafranca, Melissa R. Makris, Maria Jesus Garrido Bauerle, Roderick V. Jensen, Willard H. Eyestone

Regeneration Rosetta: An interactive web application to explore regeneration-associated gene expression and chromatin accessibility
Andrea Rau, Sumona Dhara, Ava Udvadia, Paul Auer

Research practice & education

Postdoc X-ray in Europe 2017 Work conditions, productivity, institutional support and career outlooks
Maria José Ribeiro, Ana Fonseca, Mariana Moura Ramos, Marta Costa, Konstantina Kilteni, Lau Møller Andersen, Lisa Harber-Aschan, Joana A. Moscoso, Sonchita Bagchi, European Network of Postdoctoral Associations

The Increasing Importance of Training Awards in the Careers of Early-Stage Biomedical Academic Researchers
Christopher L. Pickett

A research institution framework for publishing open code to enable reproducible science
Thomas R Etherington, Ben Jolly, Jan Zörner, Nick Spencer

To Tweet or Not to Tweet, That is the Question: A Randomized Trial of Twitter Effects on Article Engagement in Medical Education
Lauren A. Maggio, Todd C. Leroux, Anthony R. Artino Jr.

Revisiting the decay of scientific email addresses
Raul Rodriguez-Esteban, Dina Vishnyakova, Fabio Rinaldi

opentsv prevents the corruption of scientific data by Excel
Peter De Rijk, Svenn D’Hert, Mojca Strazisar

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How do genes and their environment interact during development and evolution to generate phenotypic diversity? To answer these questions in the Miura lab, by focusing on diverse animal taxa, we are studying physiological and developmental mechanisms of phenotypic changes in animal life cycles in response to environmental shifts. By the way, I’m Kohei Oguchi, a third year PhD Candidate and a member of Toru Miura’s lab at Tokyo University. Among diverse animal taxa, we have been especially focusing on social insects, “termites”.

Termites

Termites are insects belonging to a major group of social insects with divisions of labors among morphologically and behaviorally differentiated individuals (i.e., castes). In termite colonies, although all individuals share the same genetic background, there are several types of castes such as reproductives, workers and soldiers (Fig. 1A, B). These caste differentiations and caste ratios are regulated by individual interactions among colony members to organize highly sophisticated societies. Therefore, researches on termites help us to understand how genes and environments interact during development, i.e., caste differentiation, and how this interaction generates novel phenotypes, i.e., castes.

Recently, we identified a single gene which is responsible for the mandibular elongation that are seen specifically during soldier differentiation (Fig. 2A). To find genes specifically expressed in mandibles during the soldier differentiation processes, we performed gene expression analysis by RT-qPCR and immunostaining, and finally unraveled that dachshund (dac) was the gene we wanted to know (Fig. 2B). Consistently, RNA interference of dac expression inhibited the soldier-specific mandibular elongation (Fig. 2C).

Moreover, we revealed that dac expression was regulated under hormonal factors and Hox genes (Sugime et al., 2019; Fig. 2D). In some previous research, interactions among colony members are known to trigger the physiological changes such as the elevation of juvenile hormone titers leading to soldier differentiation (e.g. Cornette et al., 2008). In addition to JH, insulin signaling is also shown to be responsible for soldier morphogenesis (Hattori et al., 2013). Depletion of juvenile hormone receptor, insulin receptor or particular Hox genes all lead to reduced dac expression, shedding light on the epistatic relationships regulating the dac activity. Therefore, our study strongly suggests that the cross talks between temporal factors, i.e., hormonal pathways, and spatial factors, i.e., Hox genes, lead the caste-specific developmental modifications that are seen during caste differentiation in termites.

Typical day

To achieve these findings, in a typical day, we spend a lot of time on the workbench with several types of termite samples. For gene expression and immunostaining analysis we use several pieces of equipment such as RT-qPCR and a confocal laser microscope (Fig. 3A, B). We also spend on time with live termite individuals for behavioral observations and experimental manipulations such as caste induction and micro injection (Fig. 3C).

In our focal termite species damp-wood termite Hodotermopsis sjostedti, several castes can easily be induced. In the reproductive caste induction, we manipulate sex and caste ratio of experimental colonies. On the other hand, soldier differentiation can be easily induced by the application of juvenile hormone. In addition, we often have discussions and seminars to discuss our research progresses and experimental plans (Fig. 3D). In every May, we go for collection trips for termite colonies to the Yakushima Island, which is a subtropical island located south of Kyushu, Japan.

Field day in the forest

Our focal termite species is the damp-wood termite Hodotermopsis sjostedti, that lives in rotten trees as its common name suggests. In Japan, this species is distributed in a subtropical forest of southern islands. My supervisor, Prof. Toru Miura, has been sampling termite colonies at Yakushima island every year for nearly 20 years. Soon after arrival Yakushima island, we discuss about schedules and searching area with a spread map. After discussion, we entry the forest and search the rotten trees. We walk and climb through the forest carefully to search for termite colonies, in addition to avoid any dangerous animals such as Mamushi pit vipers (Fig. 4A). When we break rotten trees with a hammer, we occasionally find termite individuals (Fig. 4B). Then, we cut and split the log to find a whole termite colony, that is then separated into containers, by cutting the wood with a saw and an axe. Sometimes, giant centipedes appear from the log (Fig. 4C). During the field sampling we spend a whole day as if we are lumberjacks. To avoid mixing colonies, we carefully labeled the colony number and identification, and send them to our laboratory. After such physical labour, we have fun by bathing in hot springs and drinking “Mitake”, traditional distilled spirit.

Field day in the ocean

Recently, our lab moved to Misaki Marine Biological Station at the University of Tokyo (Fig. 5A, B) from Hokkaido. Two years ago, our environment was largely changed to marine laboratory, so the focus of our studies has expanded to fascinating marine animals which provide us tremendous implications on development and evolution. We are now studying diverse taxa across animal phyla, and trying to establish rearing systems for future analysis to reveal physiological and developmental aspects of flexible phenotypic changes in animal life cycles.

Misaki Marine Biological Station is one of the oldest marine stations in the world (since 1886). It is located at the tip of the Miura Peninsula in Kanagawa Prefecture, facing the Sagami Bay that shows interesting geological features and a rich diversity of marine fauna (Fig. 5A, C). We are constantly sampling diverse animal species from the ocean throughout a year. We collect a number of marine creatures by walking with waders, snorkeling or scuba diving (Fig. 6A). After sampling, we maintain those creatures in the lab to use for experiments. Now, we are working on ten species of animals belonging to eight phyla (Fig. 6B).

References

Cornette R, Gotoh H, Koshikawa S, Miura T (2008) Juvenile hormone titers and caste differentiation in the damp-wood termite Hodotermopsis sjostedti (Isoptera, Termopsidae). Journal of Insect Physiology 54:6

Hattori, A, Sugime, Y, Sasa, C, Miyakawa, H, Ishikawa, Y, Miyazaki, S, Okada, Y, Cornette, R, Lavine, LC, Emlen, DJ, Koshikawa, S, Miura, T (2013) Soldier morphogenesis in the damp‐wood termite is regulated by the insulin signaling pathway. J. Exp. Zool. (Mol. Dev. Evol.) 320B: 295– 306.

Sugime Y, Oguchi K, Gotoh H, Hayashi Y, Matsunami M, Shigenobu S, Koshikawa S, Miura T (2019) Termite soldier mandibles are elongated by dachshund under hormonal and Hox gene controls. Development 146: dev171942.

Be sure to check out the other 40 (!) articles in our ‘A Day in the Life‘ series

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‘Let your science guide you’ – An inspiring interview with Professor Anne Ferguson-Smith, a mammalian developmental geneticist. Professor Ferguson-Smith is the Head of the Department of Genetics at the University of Cambridge and a Fellow of Darwin College, Cambridge.

Professor Ferguson-Smith is an authority on genomic imprinting and the epigenetic control of genome function in health and disease, and is recognised for her work on parental-origin effects and epigenetic mechanisms. Her work has uncovered epigenetically regulated processes in development and over the life course, and identified key in vivo mechanisms involved in the maintenance of epigenetic states. She also explores communication between the environment and the genome with implications for health, disease and inheritance.

The DanStem podcast channel aims at providing a voice to the talented people who are behind the microscopes, the equipment or computers; we encourage them to share their passions, hobbies and unique career paths. In each episode, we will bring forward interesting, insightful and inspiring stories, where our guests share their personal experiences and give career-related advice.

(2 votes)

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The Company of Biologists’ journals – Development, Journal of Cell Science, Journal of Experimental Biology and Disease Models & Mechanisms – offer Travelling Fellowships of up to £2,500 to graduate students and post-doctoral researchers wishing to make collaborative visits to other laboratories. These are designed to offset the cost of travel and other expenses. There is no restriction on nationality.

They really are an amazing opportunity for ECRs to learn new things, meet new people and travel to new places.

The current round of Travelling Fellowships closes on 31 May (for travel > 15 July 2019)

Find out more here:

biologists.com/travelling/fellowships

Also learn more about what the Fellows get up to in their posts for the Node:

thenode.biologists.com/tag/travelling-fellowship/

(1 votes)

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This interview, the 63rd in our series, was recently published in Development

Butterfly eyespots are striking examples of animal patterning, but their developmental origins are still relatively poorly understood. A new paper in Development– the result of a collaboration between two Singapore-based labs – now combines CRISPR-Cas9 gene targeting with theoretical modelling to address the role of the Distal-less transcription factor in eyespot patterning. We caught up with co-first authors Heidi Connahs and Sham Tlili, and their respective supervisors Timothy Saunders (Assistant Professor at the Mechanobiology Institute, National University of Singapore) and Antónia Monteiro (Associate Professor at the Department of Biological Sciences, National University of Singapore and Yale-NUS College) to find out more about the story.

Tim and Antónia, can you give us your scientific biography and the questions your labs are trying to answer?

AM I was trained in population genetics and developmental biology, and have been trying to figure out how eyespot patterns develop on the wings of butterflies for most of my career, including investigating their origin, their evolution in number and also their ability to change in size with changes in environmental cues such as temperature. We have also been addressing how males and females use these eyespots in sexual signalling and in evading predators.

TS I was trained in theoretical physics but moved to developmental biology in 2007. Initially, I was interested in developing mathematical models, particularly of morphogen gradients, to understand how developing organisms reliably form, despite the presence of temperature variations and other natural fluctuations. I realised that access to experimental data was critical, and so I learnt Drosophila genetics and imaging during a post-doc at the European Molecular Biology Laboratory (Heidelberg, Germany). I have had my own lab since 2013 at the Mechanobiology Institute where we primarily focus on how complex organ shape emerges during development. We use both Drosophila and zebrafish embryogenesis to perform quantitative live imaging of organ formation. The lab also incorporates mathematical modelling and image analysis, to build a deeper understanding of how tissues form complex morphological shapes.

And Heidi and Sham: how did you each come to join your respective labs, and what drives your research?

HC During my PhD, I became fascinated with butterfly wing patterns and their eyespots in particular, so I was already reading a lot of Antonia’s work. And about 18 months before the end of my PhD, I attended a careers seminar where the speaker said that if there was someone we really wanted to post-doc with, we should just go ahead and contact them. So, I emailed Antonia right away and sent her my CV. I got lucky, because a semester before I graduated she contacted me and said she had funding for a postdoc and asked if I was still interested, and of course I said yes! Mostly what drives my research is a desire to understand how butterfly wing patterns develop, and specifically to identify the developmental processes that generate eyespot diversity.

ST I was trained as a physicist and enjoy doing both experimental work and modelling. I am especially interested in biological problems where spatial components play a role, and this necessitates the generation of quantitative maps of quantities such as cellular movements. I completed my PhD in Paris working on the mechanical properties of cell aggregates and cell monolayers. During the last year of my PhD, I had started to think about doing a post-doctoral work on more in vivosystems while keeping a quantitative biophysics approach. I discovered Tim through his website: he had just started his group at the Mechanobiology Institute. I was motivated by the highly interdisciplinary component of his group and by the fact that he was trained as a theoretical physicist developing experimental aspects in the lab. I was finally convinced to join his lab after meeting all the members of the lab during my interview.

How did your two labs come to collaborate on this project?

AM I think we started this collaboration via an undergraduate student, Trisha Loo, who joined Tim’s lab with an interest in modelling and was also doing some wet lab work in my lab. But the collaborative work really got going when we started getting very interesting Distal-less (Dll) crispants, such as butterflies with split eyespot centres, that really begged for modelling of potential morphogenetic processes that were differentiating those centres.

TS Antonia and I first met at a department faculty retreat. On the bus journey to the venue, we discussed patterning and complexity. We realised there was potential synergy between our labs work, and so we jointly took on Trisha to explore mathematical modelling of eyespot centre specification. The project then grew from there, with Heidi and Sham joining, who significantly pushed forward the science. Pleasingly, Tricia is now a PhD student in my lab, doing theory and image analysis – a large change from her undergraduate studies in biology!

Can you give us the key results of the paper in a paragraph?

AM The paper shows that mutations in different exons of the gene Dll affect the morphogenetic process that differentiates the cells at the centre of an eyespot pattern. Close examination of these crispants suggests that Dll is involved in a reaction-diffusion process where continuous variation in Dll levels can lead to eyespots appearing on a wing sector, to eyespots splitting into two, to finally acquiring a tear-drop shape.

TS For me, a key result of the paper is the use of modelling to describe complex phenotypes. The crispants created a diverse range of phenotypes and our model was able to explain all these observations with minimal changes.

ST I would add that modelling the spatial component of the problem was critical in this case to make sense of the complex eyespot shapes obtained.

HC Our work shows that, in Bicyclus anynana, Dll is required for eyespot formation and it also appears to have other roles such as in regulating melanin pigmentation and scale development. The experimental and modelling work suggests that different eyespot phenotypes can be explained by variation in levels of Dll expression. Our findings lead us to conclude that, as Dll expression levels decrease, eyespots become smaller or disappear altogether. However, when Dll levels increase, this leads to the duplication of eyespot centres resulting in extra eyespots developing on the wing.

Your experiments demonstrate exon-skipping/gain-of-function phenotypes from certain CRISPR-induced mutations in Dll. Do you think this is a widespread issue in the field?

AM This exact same Dll exon-skipping phenomenon has recently been shown in sepsid flies, leading to the occurrence of ectopic sternite brushes (Rajaratnam et al., 2018), and it has also been documented in other studies using cell lines (Kapahnke et al., 2016; Lalonde et al., 2017; Mou et al., 2017). What is still unclear to us is the extent that natural variation in exon skipping takes place in natural populations to alter gene function from a reduced or loss-of-function to a gain-of-function outcome.

HC There does seem to be a growing awareness now of the potential for CRISPR to induce exon skipping, and also the importance of sequencing not only the genomic DNA but the mRNA from crispants.

Why might Dll lacking exon 2 induce such weird and wonderful phenotypes?

AM: We still don’t know. The Dll truncated protein, lacking exon 2 but still containing a functioning homeobox, might be more stable and resistant to degradation, mimicking a gain-of-function phenotype.

HC Or perhaps the truncated 5′UTR increases the translation efficiency of the protein. More research is needed to understand the properties of this truncated version of Dll, and this will probably require using Drosophila transgenics to express the truncated protein.

Your theoretical model can replicate eyespot formation and Dll mutant phenotypes: do you think it might be extended to a general mechanism for how organisms make spots?

HC, ST, TS & AM Perhaps, but morphogenetic processes in the insect epidermis are largely considered a bit different from those taking place in the skin of mammals such as leopards or fish. In vertebrates, cells containing pigment molecules actually move about to take their place in a field of cells, whereas in insects, the cells are primarily differentiated in situ via interpretations of local morphogen gradients, etc. We are more excited with the idea that the models developed in this paper could help us understand limb specification in the thorax of insects via similar mechanisms.

When doing the research, did you have any particular result or eureka moment that has stuck with you?

HC When I found my first crispant which had the ectopic eyespots, that was a big eureka moment for me. Also, when I got back some sequencing results and realized that exon 2 had been spliced out, that was very exciting. I had to look at the results multiple times before I could believe it.

ST We first investigated how the classical Gierer-Meinhardt activator-inhibitor model could explain the Dllcrispants. Although this model was giving interesting results, we were struggling to find a unique set of parameters that could explain the ensemble of the crispants phenotypes. Then, Antonia motivated us to look for a model where the morphogens are anti-colocalised instead of colocalised – to be in closer agreement with the experimental data. Shortly after implementing the Gray-Scott model, I found that this model easily generated phenotypes strikingly similar to the crispants phenotypes. This was a very satisfying moment.

And what about the flipside: any moments of frustration or despair?

HC Yes, I definitely had a lot of those moments too. Initially when I started doing the CRISPR experiments, we had a lot of trouble getting it to work and so for several months there was this heart-pounding moment each time I went to check if there were any butterflies with interesting wing phenotypes and it was very disheartening to see normal looking butterflies. Eventually we realized it was the cas9 protein, and once we ordered a new one, the experiments finally worked: that was a huge relief!

ST Maybe after sending the first draft versions, when some readers were not reading the modelling part of the story and thinking the crispants phenotypes were just not making any sense. I think that, in this story, the modelling and experimental aspects are tightly entangled. These criticisms made me realise how important it is to make the model as pedagogical as possible in a highly interdisciplinary context.

I had to look at the results multiple times before I could believe it

So what next for you two after this paper?

HC I am now focusing on targeting the enhancers of Dllusing CRISPR so we can try to understand the origins of butterfly eyespots by identifying pleiotropic enhancers. This has been quite a difficult project to work on as using CRISPR to target enhancers comes with its own unique set of challenges, but we are now starting to get some preliminary results that look quite promising!

ST I just moved back to France after three great years in Tim’s group. I started a new post-doc on embryonic stem cell aggregates mimicking early mammalian development. This project will combine tissue mechanics and potentially morphogen reaction-diffusion again!

Where will this work take the Saunders and Monteiro lab? Any plans for further collaborations?

AM Would love to collaborate further with Tim’s lab. The insights they provided into our crazy looking crispant mutants were amazing. We are now mutating other genes that are also expressed in eyespots and we are observing similar eyespot splits, etc. The reaction-diffusion process seems to involve multiple genes and we might need to model the action of these genes as well.

TS This work has nicely gone alongside our lab’s study on complex shape emergence. Both patterning and mechanics play important roles in organ formation. In the future, we are hoping to integrate reaction-diffusion modelling with mechanobiology. Of course, I’d be delighted to work further with Antonia – the butterfly is an awesome system.

Finally, let’s move outside the lab – what do you like to do in your spare time in Singapore?

AM I love to hike through Singapore’s forested parks on the weekends. My husband and I usually do a 10 km trek that ends in VivoCity – a mall with many lunch options!

TS I climb with my wife regularly and much of my weekend is spent exploring Singapore with our 6-year-old daughter.

HC Usually on the weekends I enjoy relaxing with my boyfriend and visiting different science/art/nature-themed attractions or exhibitions in Singapore. I also enjoy watercolour painting and keeping aquarium fish.

ST In Singapore, I really enjoyed walking in the parks along the harbour which gave a really nice view of the sea, Indonesian islands in the horizon and all these coloured container ships coming from all over the world.

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The Clark  and Monaghan Laboratory at Northeastern University are seeking a postdoc for an NIH-funded project to image acetylcholine in the mouse peripheral nervous system. This project is an exciting opportunity to use novel fluorescent imaging to image neural communication in vivo to understand nerve-organ interactions. Experience in mouse neurobiology and in vivo imaging is desirable.

Interested candidates should email a cover letter describing their research background and CV to j.monaghan@northeastern.edu.

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We are happy to announce the launch of preLists, a new initiative within preLights where early-career researchers curate lists of preprints for the community. These lists follow two main themes: preprints on a specific topic or preprints which have been presented at scientific meetings. preLighters can also add brief one-liner summaries to each preprint, and topic-specific lists continuously get updated as new studies come out. So what was the thinking behind starting this new experiment?

When we launched preLights fifteen months ago, one of our main aims was to facilitate preprint commenting. With four-hundred preLight posts published so far, and over a third of them containing comments from authors, we hope to have played a small role in promoting discussion. We also wanted preLights to become a platform that helps scientists navigate the ever-increasing preprint literature.  While preLighters contribute new posts each week to the website, due to the sheer volume of newly posted preprints, they can only cover a fraction of the important new studies deposited on bioRxiv. With preLists, we want to provide an even richer selection of interesting work, grouped into well-defined topics, including technologies (e.g. preprints on CRISPR technology, biomolecular NMR or microscopy)  or narrower research areas (e.g. preprints on zebrafish immunology, cellular metabolism and mitochondria  or antimicrobials).

In addition, preLists will also feature preprints that were presented at conferences, providing a useful service for both attendees as well as those who were not able to make it to the meeting. An encouraging trend is that researchers are more willing to discuss their non-peer-reviewed work at scientific meetings because they have posted, or are in the process of posting, a preprint on the findings. With well over a hundred preLighters who work in different fields, we hope to be able to cover a good number of conferences. For some first examples, take a look at the preLists from the BSCB/BSDB Meeting 2019, Biophysical Society Annual Meeting 2019, 1st Crick-Beddington Developmental Biology Symposium 2019 and the ASCB/EMBO Meeting 2018.

We believe that preLists will nicely complement preLight posts, and to further support this, the two will cross-link to each other on the website. We hope you will find this new feature on preLights useful, and if you would like to take a part in writing preLights and curating preLists, apply to join our team!

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Since the Young Embryologist Network (YEN) was established in 2008, its annual conference grows from strength to strength, and thanks to the introduction of travel grants in 2017, the YEN meeting now welcomes an international delegation of attendees studying a variety of developmental problems. YEN conferences are special because they organised by early-career researchers for early-career researchers, which creates a distinctive atmosphere of support, collaboration and discussion. I attended the YEN meetings many times during my PhD and PostDoc, and last week I was happy to join again on behalf of Development to celebrate the 11^th annual conference. It was the second year that the one-day event was hosted at the Francis Crick Institute, where it featured three invited speakers, 12 selected speakers, around 30 poster presentations and a panel discussion on careers.

One of the common themes of the day was morphogenesis. Florence Giger presented on the dynamics of forebrain neurulation, using live-imaging to investigate myosin localisation during zebrafish neural tube closure. At the opposite end of the embryo, Lewis Thomson explored the dynamics of the zebrafish presomitic mesoderm, which decreases in every dimension during axis elongation. Similarly, Toby Andrews translated morphology into quantitative data in order to understand axis elongation in amphioxus, and used lineage-tracing experiments to identify axial progenitor cells. Sally Lowell (one of the invited speakers) also quantified morphogenesis and, in her opening talk, revealed new tools to measure epithelial formation in the primitive streak¹. Sally explained how morphological changes to tissues can help cells commit to changes in gene expression by manipulating the 3D organisation of epiblast stem cells with micropatterns². You can find out more about her work in “The people behind the papers” interview with Sally, and her colleagues and collaborators, here on the Node.

In recent years, the YEN conferences have hosted a celebration of the memory of Sammy Lee, a prominent scientist in the field of IVF and a great supporter of early career researchers. This year’s Sammy Lee Memorial Lecture was given by keynote speaker Takashi Hiiragi, who returned to the role of forces during development by demonstrating the role of cortical tension in mouse blastocoel self-organisation and fluid cavities in regulating tissue size^3,4. Also working in the pre-implantation embryo, Claudia Gerri showed a conserved molecular cascade during blasocyst formation in the mouse, human and cow. Claudia received the Sammy Lee Award for her talk, which is presented to one of the speakers for an “outstanding piece of research”. The medal was awarded by Sammy’s wife Karen Lee, who was one of the judges along with David Wilkinson and Karen Liu. Also keeping in early mammalian development, Sergio Menchero explained the role of Notch signalling in driving the transition for pre-implantation differentiation⁵, and you can read the story behind the paper here on the Node. Notch also featured in Valeria Scagliotti‘s talk on the pituitary gland, where she showed that overexpression of Dlk1 increases the proliferation of anterior pituitary gland progenitors.

Many of the speakers are interrogating how cells make decisions. Systems biologist and invited speaker Jordi Garcia-Ojalvo proposed using recurrent neural networks to explain how gene regulatory networks can achieve “memory” of their past multidimensional inputs during differentiation⁶. Noelia Muñoz-Martín discussed the role of Myc⁷ and MEIS transcription factors in murine cardiac development, and showed that knockdown of MEIS genes affects calcium signalling. Joana Silva discussed the requirement of the mRNA capping enzyme, CMTR1, during pluripotent cell differentiation in embryoid bodies, and Eleni Chrysostomou presented her research in the hydroid, Hydractinia using fluorescent reporter lines to unpick the roles of SoxB family genes in the differentiation of stem cells to neurons. Sergi Junyent Espinosa revealed the neuronal-like properties of stem cells, which utilise synapse-like interactions to find their niche. Andreas Sagner revealed the dynamics of mouse spinal cord development, using single-cell sequencing data from the developing neural tube⁸ and won a runner-up prize for his talk. The second runner-up Can Aztekin discussed his work — also involving single-cell sequencing — to identify a new population of cells (ROCs) required for Xenopus tail regeneration⁹.

The talks concluded with a careers panel discussion featuring Marta Gritti (Senior Editor at EBioMedicine, Elsevier), Andy Powell (Crick, GSK Biomedical LinkLabs), Graham Mills (Co-founder and Managing Director of Techspert), and Silvia Santos (Group Leader at the Crick). The panel talked about their career paths and the responsibilities in their current roles, as well as answering questions from the audience about job security, the necessity of moving abroad, the value of internships, the first steps to starting a new career, and opportunities to return to academia. Overall, the panel agreed that we should do what we like doing, for as long as we want — or are able — to do it!

For the first time, all attendees were invited to vote for their favourite posters. The first place poster prize was awarded to Yan Liang for her poster on appendage repression during the evolution of crustaceans and insects — well done! Congratulations to the runners up: Cato Hastings for her poster on mathematical modelling of the primitive streak and Andrea Szydlo-Shein for her poster on neuronal organisation in the zebrafish visual system.

Throughout the conference I was impressed with the good pace of the talks, the openness of speakers to share unpublished data and new ideas, and their receptiveness for feedback on their research. The conference finished with a drinks reception and the opportunity for the attendees to relax and discuss the topics of the day. Congratulations to the prize winners, thank you to the speakers and, most importantly, a huge thank you to the YEN committee for organising the meeting and all their hard work behind the scenes.

If you’d like to know more about the science during the meeting, check out the Twitter @YEN_community, the hashtags #YENconf2019 & #YEN2019, or see the associated preList!

¹Blin et al. NesSys: a novel method for accurate nuclear segmentation in 3D. bioRxiv 2018. doi: https://doi.org/10.1101/502872

²Blin et al. Geometrical confinement controls the asymmetric patterning of brachyury in cultures of pluripotent cells. Development 2018; 145: dev166025. doi: 10.1242/dev.166025

³Chan et al. Hydraulic control of embryo size, tissue shape and cell fate. bioRxiv 2018. doi: https://doi.org/10.1101/389619

⁴Kim et al. Coordination of Cell Polarity, Mechanics and Fate in Tissue Self-organization. Trends Cell Biol 2018. doi: https://doi.org/10.1016/j.tcb.2018.02.008

⁵Menchero et al. Transitions in cell potency during early mouse development are driven by Notch. eLife 2019;8:e42930. doi: 10.7554/eLife.42930

⁶Gabalda-Sagarra et al. Recurrence-based information processing in gene regulatory networks. Chaos 2018; 28(10):106313. doi: 10.1063/1.5039861

⁷ Noelia Muñoz-Martín et al. Myc is dispensable for cardiomyocyte development but rescues Mycn-deficient hearts through functional replacement and cell competition. Development 2019; 146: dev170753 doi: 10.1242/dev.170753

⁸Delile et al. Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord. Development 2019; 146: dev173807 doi: 10.1242/dev.173807

⁹Aztekin et al. Identification of a regeneration-organizing cell in the Xenopus tail. Science 2019; 364(6441), 653-658. doi: 10.1126/science.aav9996

(3 votes)

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In this episode from our series exploring 100 ideas in genetics, we’re taking a trip to London with William Bateson and discovering that the famous story about him reading Mendel’s paper on the train might not be all that it seems.

Plus, we seek the secrets of snapdragons, and learn how to build an army of MinIONs.

Listen and download now from GeneticsUnzipped.com, plus full show notes and transcripts.

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This interview, the 62nd in our series, was recently published in Development

Vascular development critically involves pruning, which helps to remodel an immature network containing excess microvessels into a mature and functioning one. The mechanisms of vascular remodelling and the relationship between the endothelial cells and the other cell types with which they are closely associated are, however, currently poorly understood. A new Development paper now demonstrates a crucial role for oxygen sensing by astrocytes in vascular remodelling of the mouse retina. We caught up with the two-author team behind the paper: research associate Li-Juan Duan and her supervisor Guo-Hua Fong, Professor of Cell Biology at the University of Connecticut Health Center, to hear more about the story.

Guo-Hua, can you give us your scientific biography and the questions your lab is trying to answer?

GHF After graduating from Hangzhou University in 1982, I attended the PhD Program in Biochemistry at the University of Illinois at Urbana-Champaign. My interest in angiogenesis began during my postdoctoral training with Martin Breitman and Janet Rossant in Toronto. After reporting the finding that Flt-1 (VEGFR1) was a negative regulator of vasculogenesis, I set up my first lab at the University of Western Ontario before relocating to where I am now (UConn School of Medicine).

Early in my career as a developmental biologist, I used mouse embryos to study vasculogenesis and angiogenesis, but since about a decade ago I have been primarily focused on mouse retinas. At the molecular level, my current focus is on oxygen sensing and hypoxia signalling because growth of blood vessels is mostly (although not exclusively) an adaptive response to tissue hypoxia. Molecules of interest include hypoxia inducible factor (HIF) 2α (also called EPAS1), a transcription factor stabilized by hypoxia that activates the expression of angiogenic factors, and prolyl hydroxylase domain (PHD) proteins (EGLNs), which sense oxygen and destabilize HIFα proteins by oxygen-dependent prolyl hydroxylation reactions.

Li-Juan: how did you come to join the Fong lab and what drives your research?

LJD With a few exceptions, almost all tissues are vascularized. Mechanisms ensuring that blood vessels are formed at the right place, right time and with right configurations are very fascinating to me. Dr Fong’s lab investigates the molecular and cellular mechanisms regulating blood vessel growth, and has contributed significantly to this rapidly advancing field. So the opportunity to be a part of team and contribute to the exciting discoveries is a major driving force for my research. Also, the potential that knowledge generated from these studies might improve angiogenesis therapies is quite energizing.

What was known about the link between astrocytes, endothelial cells and oxygen in retinal angiogenesis prior to your work?

LJD & GHF The retinal astrocytic network is situated just beneath the vascular network on the inner retinal surface, with foot processes from astrocytes wrapping around vascular endothelial cells (ECs) and supporting their survival. It was thought that the astrocytic network forms before retinal angiogenesis and serves as a template for the subsequent vascular growth. The newly formed vascular network exhibits a honeycomb pattern consisting of almost uniformly sized capillaries, separated by roundish non-vascular tissues. To gain circulatory functions, the nascent vascular plexus undergoes active remodelling to form a tree-like pattern with large trunks and smaller branches. During this process, excess microvessels are pruned away. One widely held but never formally documented view is that oxygen causes pruning by activating EC apoptosis. The other theory is that T cells interact with ECs to cause pruning. In both theories, astrocytes were not suspected to play a role in remodelling.

Can you give us the key results of the paper in a paragraph?

LJD & GHF We found that retinal astrocytes respond to changes in tissue oxygenation mostly through prolyl hydroxylase domain (PHD) protein 2, an enzyme known to use O₂ and oxoglutarate as substrates to hydroxylate transcription factors HIF1α and HIF2α, causing them to degrade. In neonatal mouse retinas, HIF2α is essential for the expansion of the astrocyte population owing to its role in maintaining astrocytes in immature and proliferative states. Angiogenesis imposes a physiological limit to the abundance of retinal astrocytes by causing O₂-dependent HIF2α degradation. As such, a proportion of the numerous capillaries generated through robust angiogenesis is unable to acquire astrocytic support and undergoes regression (pruning). In support of this theory, targeted disruption of the Phd2 gene in astrocytes led to accumulation of HIF-2α protein, expansion of retinal astrocyte population, and persistence of extra microvessels. When astrocyte growth was directly stimulated by intraocular injection of PDGFA into the eyes in wild-type mice, vascular pruning was also blocked. Based on these findings, we conclude that oxygen- and PHD2-dependent astrocyte growth arrest is a feedback mechanism to prevent runaway vascularization.

Do you have any ideas about what happens downstream of Phd2/HIFα to induce differentiation in astrocytes?

LJD & GHF We don’t really know yet, but there may be some candidates. HIF2α is known to promote the expression of Oct4, a transcription factor important for the maintenance of stem cell identity. While the astrocyte precursors may not be exactly stem cells, they might share certain features related to stem cells. So it seems to us that HIF2α-dependent expression of Oct4 might be a potential mechanism by which HIF2α helps maintain astrocytes at precursor and immature states. At this point, this idea remains highly speculative but it could be a reasonable starting point for the next step.

Does your work have any relevance to pathological contexts?

LJD & GHF Capillary dropout is a common feature in early stage diabetic retinopathy. The prevailing view at present is that capillary dropout starts with apoptosis of pericytes, a type of supporting cell that adheres to the endothelial cells. Our finding of a crucial role for astrocytes in capillary maintenance raises the question of whether the adverse effects of diabetes on retinal astrocytes might also contribute to capillary dropout? If so, the retinal astrocytes could be a novel therapeutic target for improving retinal vascular stability. In this regard, it may be interesting to note that there’s a publication indicating that retinal astrocyte abundance is decreased in diabetic rats (Ly et al., 2011).

Our findings are also related to retinopathy of prematurity (ROP), a disease associated with premature birth. Whereas pathological mechanisms underlying ROP are complicated and go beyond oxygen alone, sensitivity to oxygen is nonetheless an important component. Thus, targeting astrocytic PHD2 could provide a novel opportunity for minimizing the consequence of ROP.

When doing the research, did you have any particular result or eureka moment that has stuck with you?

LJD I guess the moment was when I found that simply injecting PDGFA into the eyes caused both expanded astrocyte populations and persistence of more microvessels, whereas injection of PBS into the contralateral eyes didn’t. These results indicated that increased astrocyte abundance alone was sufficient to block vascular pruning.

And what about the flipside: any moments of frustration or despair?

LJD Sure, plenty of them. This was actually a lengthy project. While I’ve been working on other projects in parallel, this project was on and off for nearly 6 years. While we observed the overcrowded vascularization at the very start of the project, it was rather challenging trying to explain why. Naturally, our initial attention was on VEGF, and lots of time was wasted in that direction. We couldn’t just publish overcrowded capillaries without being able to explain the underlying mechanism, so the project was really stuck for a long time until one day we realized perhaps it was simply the number of astrocytes itself rather than any specific molecule. We also ran into a lot of technical difficulties. One example was growing primary retinal astrocytes: because they could not be expanded too much, we had to pool the cells from a very large number of retinas. These are just two of the many examples.

Where will this work take the Fong lab?

GHF We will be pursuing several directions. We are interested in identifying the potential targets downstream of PHD2/HIF2α by RNA-seq, and then assessing their functionality in retinal vascular development by CRISPR/Cas9-mediated knockout. We will be also looking into potential interaction between HIF2α with a transcription factor called Nr2e1 or Tlx. We are interested in finding out whether the two transcription factors collaborate in retinal astrocytes in controlling astrocyte differentiation. We are also interested in investigating if PHD2 deficiency in astrocytes also confers protection to capillaries in disease models such as oxygen-induced retinopathy and diabetic retinopathy.

For whatever reasons, the vascular biology community has paid very little attention to astrocytes. The major focus is still on endothelial cells, and their interaction with pericytes, vascular smooth muscle cells and leukocytes. In fact, we also stumbled into this subject accidentally, but we increasingly appreciated the opportunity that fell upon us as we began to realize the importance of this cell type to vascular growth, stability and function. Because so little is known about astrocytes in the context of vascular biology, there are plenty of exciting findings to be made. In the coming years, we will be devoting much of our efforts trying to understand how astrocytes communicate with endothelial cells to regulate various aspects of vascular homeostasis.

Because so little is known about astrocytes in the context of vascular biology, there are plenty of exciting findings to be made

Finally, let’s move outside the lab – what do you like to do in your spare time in Connecticut?

LJD Spring is beautiful in Connecticut. I enjoy growing flowers, watching them blossom in the morning. There are also plenty of water reservoirs with hiking trails open to the public. I enjoy taking long walks around the lakes on weekends, especially in the spring and fall.

GHF Connecticut may not be a frequently talked-about place but it is not exactly in the middle of nowhere either – in fact the UConn School of Medicine campus is just about 2 h from Boston and New York, respectively. So it’s relatively convenient to spend a day in the weekend visiting museums or friends there, or even shopping. Also Connecticut is full of very long hiking trails at different levels of difficulty, so one could spend hours (or days if they like) hiking to fairly distant locations, with some leading all the way into neighbouring states.

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