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

The preprints this month are hosted on bioRxiv, arXiv and preprints.org – 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

Cell Biology

Modelling

Tools & Resources

Research practice & education

Developmental biology

| Patterning & signalling

Ssdp influences Wg expression and embryonic somatic muscle identity in Drosophila melanogaster
Preethi Poovathumkadavil, Jean-Philippe Da Ponte, Krzysztof Jagla

Inhibition of aryl hydrocarbon receptor signaling promotes the terminal differentiation of human erythrocytes
Yijin Chen, Yong Dong, Xulin Lu, Wanjing Li, Yimeng Zhang, Bin Mao, Xu Pan, Xiaohong Li, Ya Zhou, Quanming An, Fangxin Xie, Shihui Wang, Yuan Xue, Xinping Cai, Mowen Lai, Qiongxiu Zhou, Yan Yan, Ruohan Fu, Hong Wang, Tatsutoshi Nakahata, Xiuli An, Lihong Shi, Yonggang Zhang, Feng Ma

Insulin is expressed by enteroendocrine cells during human fetal development
Adi Egozi, Dhana Llivichuzhca-Loja, Blake McCourt, Lydia Farack, Xiaojing An, Fujing Wang, Kong Chen, Liza Konnikova, Shalev Itzkovitz

Differential growth is a critical determinant of zebrafish pigment pattern formation
Jennifer P. Owen, Christian A. Yates, Robert N. Kelsh

TopFlash transgenic quail reveals dynamic TCF/β-catenin signaling during avian embryonic development
Hila Barzilai-Tutsch, Valerie Morin, Gauthier Toulouse, Stephen Firth, Christophe Marcelle, Olivier Serralbo

In vitro endoderm emergence and self-organisation in the absence of extraembryonic tissues and embryonic architecture
Stefano Vianello, Matthias P. Lutolf

Serotonergic neuron ribosomes regulate the neuroendocrine control of Drosophila development
Lisa P. Deliu, Deeshpaul Jadir, Abhishek Ghosh, Savraj S. Grewal

Differential repression of Otx2 underlies the capacity of NANOG and ESRRB to induce germline entry
Matúš Vojtek, Jingchao Zhang, Juanjuan Sun, Man Zhang, Ian Chambers

The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic Hedgehog signalling
Leah Schembs, Ariane Willems, Kerstin Hasenpusch-Theil, James D. Cooper, Katie Whiting, Karen Burr, Sunniva M.K. Bøstrand, Bhuvaneish T. Selvaraj, Siddharthan Chandran, Thomas Theil

Naa12 compensates for Naa10 in mice in the amino-terminal acetylation pathway
Hyae Yon Kweon, Mi-Ni Lee, Max Dörfel, Seungwoon Seo, Leah Gottlieb, Thomas Papazyan, Nina McTiernan, Rasmus Ree, David Bolton, Andrew Garcia, Michael Flory, Jonathan Crain, Alison Sebold, Scott Lyons, Ahmed Ismail, Elaine Marchi, Seong-keun Sonn, Se-Jin Jeong, Sejin Jeon, Shinyeong Ju, Simon J. Conway, TaeSoo Kim, Hyun-Seok Kim, Cheolju Lee, Tae-Young Roh, Thomas Arnesen, Ronen Marmorstein, Goo Taeg Oh, Gholson J. Lyon

Developmental Regulation of Homeostatic Plasticity in Mouse Primary Visual Cortex
Wei Wen, Gina G. Turrigiano

Patterning on the move: the effects of Hh morphogen source movement on signaling dynamics
D. G. Míguez, A. Iannini, D. García-Morales, F. Casares

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age
Ralica Dimitrova, Maximilian Pietsch, Judit Ciarrusta, Sean P. Fitzgibbon, Logan Z. J. Williams, Daan Christiaens, Lucilio Cordero-Grande, Dafnis Batalle, Antonios Makropoulos, Andreas Schuh, Anthony N. Price, Jana Hutter, Rui PAG Teixeira, Emer Hughes, Andrew Chew, Shona Falconer, Olivia Carney, Alexia Egloff, J-Donald Tournier, Grainne McAlonan, Mary A. Rutherford, Serena J. Counsell, Emma C. Robinson, Joseph V. Hajnal, Daniel Rueckert, A. David Edwards, Jonathan O’Muircheartaigh

Connectomes across development reveal principles of brain maturation
Daniel Witvliet, Ben Mulcahy, James K. Mitchell, Yaron Meirovitch, Daniel R. Berger, Yuelong Wu, Yufang Liu, Wan Xian Koh, Rajeev Parvathala, Douglas Holmyard, Richard L. Schalek, Nir Shavit, Andrew D. Chisholm, Jeff W. Lichtman, Aravinthan D.T. Samuel, Mei Zhen

Homothorax Controls a Binary Rhodopsin Switch in Drosophila Ocelli
Abhishek Kumar Mishra, Cornelia Fritsch, Roumen Voutev, Richard S. Mann, Simon G. Sprecher

Genetic and chemical inhibition of autophagy in zebrafish induced myeloproliferation
Kazi Md Mahmudul Hasan, Xiang-Ke Chen, Zhen-Ni Yi, Jack Jark-Yin Lau, Alvin Chun-hang Ma

The asymmetric Pitx2 regulates intestinal muscular-lacteal development and protects against fatty liver disease
Shing Hu, Aparna Mahadevan, Isaac F. Elysee, Joseph Choi, Nathan R. Souchet, Gloria H. Bae, Alessandra K. Taboada, Gerald E. Duhamel, Carolyn S. Sevier, Ge Tao, Natasza A. Kurpios

The atypical RNA-binding protein TAF15 regulates dorsoanterior neural development through diverse mechanisms in Xenopus tropicalis
Caitlin S. DeJong, Darwin S. Dichmann, Cameron R. T. Exner, Yuxiao Xu, Richard M. Harland

Estrogen regulates early embryonic development of the olfactory sensory system via estrogen-responsive glia
Aya Takesono, Paula Schirrmacher, Aaron Scott, Jon M. Green, Okhyun Lee, Matthew J. Winter, Tetsuhiro Kudoh, Charles R. Tyler

Chronic opioid treatment arrests neurodevelopment and alters synaptic activity in human midbrain organoids
Hye Sung Kim, Yang Xiao, Xuejing Chen, Siyu He, Jongwon Im, Moshe J. Willner, Michael O. Finlayson, Cong Xu, Huixiang Zhu, Se Joon Choi, Eugene V. Mosharov, Hae-Won Kim, Bin Xu, Kam W. Leong

Polypeptides IGF-1C and P24 synergistically promote osteogenic differentiation of bone marrow mesenchymal stem cells in vitro through the p38 and JNK signaling pathways
Gaoying Ran, Wei Fang, Lifang Zhang, Yuting Peng, Jiatong Li, Xianglong Ding, Shuguang Zeng, Yan He

Amyloid precursor protein localises to ependymal cilia in vertebrates and is required for ciliogenesis and brain development in zebrafish
Jasmine Chebli, Maryam Rahmati, Tammaryn Lashley, Birgitta Edeman, Anders Oldfors, Henrik Zetterberg, Alexandra Abramsson

Notch pathway is required for protection against heat-stress in spermatogonial stem cells
Omar D. Moreno Acosta, Agustín F. Boan, Ricardo S. Hattori, Juan I. Fernandino

In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation
Bethan Lloyd-Lewis, Francesca Gobbo, Meghan Perkins, Guillaume Jacquemin, Marisa M Faraldo, Silvia Fre

Apoptotic Find-me Signals are an Essential Driver of Stem Cell Conversion To The Cardiac Lineage
Loic Fort, Vivian Gama, Ian G. Macara

Notch-dependent Abl signaling regulates cell motility during ommatidial rotation in Drosophila
Yildiz Koca, Linh T. Vuong, Jaskirat Singh, Edward Giniger, Marek Mlodzik

EXC-4/CLIC, Gα, and Rho/Rac signaling regulate tubulogenesis in C. elegans
Anthony F. Arena, Daniel D. Shaye

Release of Notch activity coordinated by IL-1β signalling confers differentiation plasticity of airway progenitors via Fosl2 during alveolar regeneration
Jinwook Choi, Yu Jin Jang, Catherine Dabrowska, Elhadi Iich, Kelly V. Evans, Helen Hall, Sam M. Janes, Benjamin D. Simons, Bon-Kyoung Koo, Jonghwan Kim, Joo-Hyeon Lee

Reciprocal EGFR signaling in the Anchor Cell ensures precise inter-organ connection during C. elegans vulval morphogenesis
Silvan Spiri, Simon Berger, Louisa Mereu, Andrew DeMello, Alex Hajnal

Synergistic TOR and ERK inhibition mitigates the hereditary haemorrhagic telangiectasia-like phenotype and excess kugel formation in endoglin mutant zebrafish
Ryan O. Snodgrass, Helen M. Arthur, Timothy J.A. Chico

Gene-teratogen interactions influence the penetrance of birth defects by altering Hedgehog signaling strength
Jennifer H. Kong, Cullen B. Young, Ganesh V. Pusapati, F Hernán Espinoza, Chandni B. Patel, Francis Beckert, Sebastian Ho, Bhaven B. Patel, George C. Gabriel, L. Aravind, J Fernando Bazan, Teresa M. Gunn, Cecilia W. Lo, Rajat Rohatgi

GLI transcriptional repression is inert prior to Hedgehog pathway activation
Rachel K. Lex, Weiqiang Zhou, Zhicheng Ji, Kristin N. Falkenstein, Kaleigh E. Schuler, Kathryn E. Windsor, Joseph D. Kim, Hongkai Ji, Steven A Vokes

FGF/ERK autocrine signaling is enhanced by NANOG in a subpopulation of pluripotent stem cells to execute autoregulation and induce heterogeneity
Hanuman T Kale, Rajendra Singh Rajpurohit, Debabrata Jana, Vishnu V Vijay, Mansi Srivastava, Preeti R Mourya, Gunda Srinivas, P Chandra Shekar

Neuronal KGB-1 JNK MAPK signaling regulates the dauer developmental decision in response to environmental stress in C. elegans
Deepshikha Dogra, Warakorn Kulalert, Frank C. Schroeder, Dennis H. Kim

Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees

Emilie Gontran, Lorena Loarca, Cyrille El Khassis, Latifa Bouzhir, Dmitry Ayollo, Elsa Mazari-Arrighi, Alexandra Fuchs, Pascale Dupuis-Williams

| Morphogenesis & mechanics

Differential adhesion regulates neurite placement via a retrograde zippering mechanism
Titas Sengupta, Noelle L. Koonce, Mark W. Moyle, Leighton H. Duncan, Nabor Vázquez-Martínez, Sarah E. Emerson, Xiaofei Han, Lin Shao, Yicong Wu, Anthony Santella, Li Fan, Zhirong Bao, William A. Mohler, Hari Shroff, Daniel A. Colón-Ramos

Acetylated microtubules are required for maintenance of the barrier between two adjacent tissues
Matthew Antel, Taylor Simao, Muhammed Burak Bener, Mayu Inaba

A midbody component homolog, too much information/prc1-like, is required for microtubule reorganization during both cytokinesis and axis induction in the early zebrafish embryo
S Nair, E.L. Welch, C.E. Moravec, R.L. Trevena, F. Pelegri

Pak1 and PP2A antagonize aPKC function to support cortical tension induced by the Crumbs-Yurt complex
Cornélia Biehler, Katheryn E. Rothenberg, Alexandra Jetté, Hélori-Mael Gaudé, Rodrigo Fernandez-Gonzalez, Patrick Laprise

Distinct spatiotemporal contribution of morphogenetic events and mechanical tissue coupling during Xenopus neural tube closure
Neophytos Christodoulou, Paris A. Skourides

High resolution dynamic mapping of the C. elegans intestinal brush border
Aurélien Bidaud-Meynard, Flora Demouchy, Ophélie Nicolle, Anne Pacquelet, Grégoire Michaux

Met-signaling Controls Dendritic Cell Migration by Regulating Podosome Formation and Function
Ahmed E.I. Hamouda, Carmen Schalla, Antonio Sechi, Martin Zenke, Thomas Hieronymus

Cell-matrix adhesion contributes to permeability control in human colon organoids
James Varani, Shannon D. McClintock, Muhammad N. Aslam

Cell adhesions link subcellular actomyosin dynamics to tissue scale force production during vertebrate convergent extension
Robert J. Huebner, Shinuo Weng, Chanjae Lee, Sena Sarıkaya, Ophelia Papoulas, Rachael M. Cox, Edward M. Marcotte, John B. Wallingford

Convergent extension requires adhesion-dependent biomechanical integration of cell crawling and junction contraction
Shinuo Weng, Robert J. Huebner, John B. Wallingford

A new approach to measure forces at junction vertices in an epithelium
Clémentine Villeneuve, Samuel Mathieu, Emilie Lagoutte, Bruno Goud, Philippe Chavrier, Jean-Baptiste Manneville, Carine Rossé

Pressure and curvature control of contact inhibition in epithelia growing under spherical confinement
Ilaria Di Meglio, Anastasiya Trushko, Pau Guillamat, Carles Blanch-Mercader, Aurélien Roux

Mechanical Stimulation via Muscle Activity is Necessary for the Maturation of Tendon Multiscale Mechanics during Embryonic Development
Benjamin E Peterson, Rebecca A. Rolfe, Allen Kunselman, Paula Murphy, Spencer E. Szczesny

Laminin-binding Integrins Regulate Angiogenesis by Distinct and Overlapping Mechanisms in Organotypic Cell Culture Models
Hao Xu, Susan E LaFlamme

Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear
Sarah Baxendale, Esther C. Maier, Nikolaus D. Obholzer, Sarah Burbridge, Joseph Zinski, Francesca B. Tuazon, Nicholas J. van Hateren, M. Montserrat Garcia Romero, Mar Marzo, Kazutomo Yokoya, Robert D. Knight, Sean G. Megason, Mary C. Mullins, Tanya T. Whitfield

Characterisation of the transcriptional dynamics underpinning the function, fate, and migration of the mouse Anterior Visceral Endoderm
Shifaan Thowfeequ, Jonathan Fiorentino, Di Hu, Maria Solovey, Sharon Ruane, Maria Whitehead, Bart Vanhaesebroeck, Antonio Scialdone, Shankar Srinivas

IFT20 is critical for early chondrogenesis during endochondral ossification
Hiroyuki Yamaguchi, Megumi Kitami, Karin H. Uchima Koecklin, Li He, Jianbo Wang, Daniel S. Perrien, William R. Lagor, Yoshihiro Komatsu

| Genes & genomes

Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration
Matthew E. Ochs, Rebecca McWhirter, Rob Unckless, David Miller, Erik A Lundquist

A comprehensive series of temporal transcription factors in the fly visual system
Nikolaos Konstantinides, Anthony M. Rossi, Aristides Escobar, Liébaut Dudragne, Yen-Chung Chen, Thinh Tran, Azalia Martinez Jaimes, Mehmet Neset Özel, Félix Simon, Zhiping Shao, Nadejda M. Tsankova, John F. Fullard, Uwe Walldorf, Panos Roussos, Claude Desplan

Expansion of RNA sequence diversity and RNA editing rates throughout human cortical development
Ryn Cuddleston, Laura Sloofman, Lindsay Liang, Enrico Mossotto, Xuanjia Fan, Minghui Wang, Bin Zhang, Jiebiao Wang, Nenad Sestan, Bernie Devlin, Kathryn Roeder, Joseph D. Buxbaum, Stephan J. Sanders, Michael S. Breen

AP-2α and AP-2β cooperatively function in the craniofacial surface ectoderm to regulate chromatin and gene expression dynamics during facial development
Eric Van Otterloo, Isaac Milanda, Hamish Pike, Hong Li, Kenneth L Jones, Trevor Williams

A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing
Hailun Zhu, Sihai Dave Zhao, Alokananda Ray, Yu Zhang, Xin Li

Heterogeneity and molecular programming of progenitors for motor neurons and oligodendrocytes
Lingyan Xing, Rui Chai, Jiaqi Wang, Jiaqi Lin, Hanyang Li, Yueqi Wang, Biqin Lai, Junjie Sun, Gang Chen

A DNA Replication-Independent Function of the pre-Replication Complex during Cell Invasion in C. elegans
Evelyn Lattmann, Ting Deng, Michael Walser, Patrizia Widmer, Charlotte Rexha-Lambert, Vibhu Prasad, Ossia Eichhoff, Michael Daube, Reinhard Dummer, Mitchell P. Levesque, Alex Hajnal

CDK12 is Necessary to Promote Epidermal Differentiation through Transcription Elongation
Jingting Li, Manisha Tiwari, Yifang Chen, George L. Sen

Systematic reconstruction of the cellular trajectories of mammalian embryogenesis
Chengxiang Qiu, Junyue Cao, Tony Li, Sanjay Srivatsan, Xingfan Huang, Diego Calderon, William Stafford Noble, Christine M. Disteche, Malte Spielmann, Cecilia B. Moens, Cole Trapnell, Jay Shendure

Identification of enamel knot gene signature within the developing mouse molar
Emma Wentworth Winchester, Justin Cotney

Spatial cell type mapping of the oligodendrocyte lineage in the mouse juvenile and adult CNS with in situ sequencing
Markus M. Hilscher, Christoffer Mattsson Langseth, Petra Kukanja, Chika Yokota, Mats Nilsson, Gonçalo Castelo-Branco

Application of ATAC-Seq for genome-wide analysis of the chromatin state at single myofiber resolution
Korin Sahinyan, Darren M Blackburn, Marie-Michelle Simon, Felicia Lazure, Tony Kwan, Guillaume Bourque, Vahab D Soleimani

A putative de novo evolved gene required for spermatid chromatin condensation in Drosophila melanogaster
Emily L. Rivard, Andrew G. Ludwig, Prajal H. Patel, Anna Grandchamp, Sarah E. Arnold, Alina Berger, Emilie M. Scott, Brendan J. Kelly, Grace C. Mascha, Erich Bornberg-Bauer, Geoffrey D. Findlay

Klf5 establishes bi-potential cell fate by dual regulation of ICM and TE specification genes
Martin Kinisu, Yong Jin Choi, Claudia Cattoglio, Ke Liu, Hector Roux de Bezieux, Raeline Valbuena, Nicole Pum, Sandrine Dudoit, Haiyan Huang, Zhenyu Xuan, Sang Yong Kim, Lin He

C. elegans TFIIH subunit GTF-2H5/TTDA is a non-essential transcription factor indispensable for DNA repair
Karen L. Thijssen, Melanie van der Woude, Carlota Davó-Martínez, Mariangela Sabatella, Wim Vermeulen, Hannes Lans

Adult fibroblasts retain organ-specific transcriptomic identity
Elvira Forte, Mirana Ramialison, Hieu T. Nim, Madison Mara, Rachel Cohn, Sandra L. Daigle, Sarah Boyd, J. Travis Hinson, Mauro W. Costa, Nadia A. Rosenthal, Milena B. Furtado

Differential Bcd activation of two hunchback promoters emerges from unified kinetics of enhancer-promoter interaction
Jingyao Wang, Shihe Zhang, Hongfang Lu, Heng Xu

X-Linked Histone H3K27 Demethylase Kdm6a Regulates Sexually Dimorphic Differentiation of Hypothalamic Neurons
Lucas E. Cabrera Zapata, Carla D. Cisternas, Camila Sosa, Maria Angeles Arevalo, Luis Miguel Garcia-Segura, María Julia Cambiasso

Environment-driven reprogramming of gamete DNA methylation occurs during maturation and is transmitted intergenerationally in salmon
Kyle Wellband, David Roth, Tommi Linnansaari, R. Allen Curry, Louis Bernatchez

ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment
Jeffrey D. Steimle, Chul Kim, Rangarajan D. Nadadur, Zhezhen Wang, Andrew D. Hoffmann, Erika Hanson, Junghun Kweon, Tanvi Sinha, Kyunghee Choi, Brian L. Black, John M. Cunningham, Kohta Ikegami, Ivan P. Moskowitz

Multivariate genome-wide association studies on the tissue compartments of human brain identify novel loci underpinning brain development and neuropsychiatric outcomes
Chun Chieh Fan, Robert Loughnan, Carolina Makowski, Diliana Pechva, Chi-Hua Chen, Donald Hagler, Wesley K. Thompson, Dennis van der Meer, Oleksandr Frei, Ole Andreassen, Anders M. Dale

Chromatin dynamics during hematopoiesis reveal discrete regulatory modules instructing differentiation
Grigorios Georgolopoulos, Nikoletta Psatha, Mineo Iwata, Andrew Nishida, Tannishtha Som, Minas Yiangou, John A. Stamatoyannopoulos, Jeff Vierstra

H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate
A. Dubois, L. Vincenti, A. Chervova, S. Vandormael-Pournin, M. Cohen-Tannoudji, P. Navarro

Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns
Tamar Shahal, Elad Segev, Thomas Konstantinovsky, Yonit Marcus, Gabi Shefer, Metsada Pasmanik-Chor, Assaf Buch, Yuval Ebenstein, Paul Zimmet, Naftali Stern

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline
Elisabeth A. Marnik, Miguel V. Almeida, P. Giselle Cipriani, George Chung, Edoardo Caspani, Emil Karaulanov, Falk Butter, Catherine S. Sharp, John Zinno, Hin Hark Gan, Fabio Piano, René F Ketting, Kristin C. Gunsalus, Dustin L. Updike

Blm Helicase Facilitates Rapid Replication of Repetitive DNA Sequences in early Drosophila Development
Jolee M. Ruchert, Morgan M Brady, Susan McMahan, Karly J. Lacey, Leigh C. Latta, Jeff Sekelsky, Eric P. Stoffregen

Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos
Elena Lo Furno, Isabelle Busseau, Claudio Lorenzi, Cima Saghira, Matt C Danzi, Stephan Zuchner, Domenico Maiorano

Identification of PAX6 and NFAT4 as the transcriptional regulators of lncRNA Mrhl in neuronal progenitors
Debosree Pal, Sangeeta Dutta, Dhanur P Iyer, Utsa Bhaduri, M.R.S Rao

Conserved Transcription Factors Control Chromatin Accessibility and Gene Expression to Maintain Cell Fate Stability and Restrict Reprogramming of Differentiated Cells
Maria A. Missinato, Sean A. Murphy, Michaela Lynott, Anaïs Kervadec, Michael S. Yu, Yu-Ling Chang, Suraj Kannan, Mafalda Loreti, Christopher Lee, Prashila Amatya, Hiroshi Tanaka, Chun-Teng Huang, Pier Lorenzo Puri, Chulan Kwon, Peter D. Adams, Li Qian, Alessandra Sacco, Peter Andersen, Alexandre R. Colas

ZFP462 targets heterochromatin to transposon-derived enhancers restricting transcription factor binding and expression of lineage-specifying genes
Ramesh Yelagandula, Karin Stecher, Maria Novatchkova, Luca Michetti, Georg Michlits, Jingkui Wang, Pablo Hofbauer, Carina Pribitzer, Gintautas Vainorius, Luke Isbel, Sasha Mendjan, Dirk Schübeler, Ulrich Elling, Julius Brennecke, Oliver Bell

MicroRNA-202 prevents precocious spermatogonial differentiation and meiotic initiation during mouse spermatogenesis
Jian Chen, Chenxu Gao, Xiwen Lin, Yan Ning, Wei He, Chunwei Zheng, Daoqin Zhang, Lin Yan, Binjie Jiang, Yuting Zhao, Md Alim Hossen, Chunsheng Han

RNAseq analysis reveals dynamic metaboloepigenetic profiles of human, mouse and bovine pre-implantation embryos
Marcella Pecora Milazzotto, Michael James Noonan, Marcia de Almeida Monteiro Melo Ferraz

| Stem cells, regeneration & disease modelling

The NF-κB pathway regulates heterochromatin at intronic young LINE-1 elements and hematopoietic stem cell gene expression during irradiation stress
Yanis Pelinski, Donia Hidaoui, François Hermetet, Anne Stolz, M’boyba Khadija Diop, Amir M. Chioukh, Françoise Porteu, Emilie Elvira-Matelot

Intestine-enriched apolipoprotein b orthologs are required for stem cell differentiation and regeneration in planarians
Lily L. Wong, Christina G. Bruxvoort, Nicholas I. Cejda, Jannette Rodriguez Otero, David J. Forsthoefel

Proliferation maintains the undifferentiated status of stem cells: the role of the planarian cell cycle regulator Cdh1
Yuki Sato, Yoshihiko Umesono, Yoshihito Kuroki, Kiyokazu Agata, Chikara Hashimoto

Investigation of Thyroid Hormone Associated Gene-Regulatory Networks during Hepatogenesis using an Induced Pluripotent Stem Cell based Model
Audrey Ncube, Nina Graffmann, Jan Greulich, Bo Scherer, Wasco Wruck, James Adjaye

Robust differentiation of human enteroendocrine cells from intestinal stem cells
Daniel Zeve, Eric Stas, Joshua de Sousa Casal, Prabhath Mannam, Wanshu Qi, Xiaolei Yin, Sarah Dubois, Manasvi S. Shah, Erin P. Syverson, Sophie Hafner, Jeffrey M. Karp, Diana L. Carlone, Jose Ordovas-Montanes, David T. Breault

Loss of Resf1 reduces the efficiency of embryonic stem cell self-renewal and germline entry
Matúš Vojtek, Ian Chambers

Hypertrophic Chondrocytes Serve as a Reservoir for Unique Marrow Associated Skeletal Stem and Progenitor Cells, Osteoblasts, and Adipocytes During Skeletal Development
Jason T. Long, Abigail Leinroth, Yihan Liao, Yinshi Ren, Anthony J. Mirando, Tuyet Nguyen, Wendi Guo, Deepika Sharma, Colleen Wu, Kathryn Song Eng Cheah, Courtney M. Karner, Matthew J. Hilton

Identification of SUMO targets required to maintain human stem cells in the pluripotent state
Barbara Mojsa, Michael H. Tatham, Lindsay Davidson, Magda Liczmanska, Emma Branigan, Ronald T. Hay

Stem cell therapy for skin regeneration using mesenchymal stem cells derived from the progeroid Werner syndrome-specific iPS cells
Shinichiro Funayama, Hisaya Kato, Hiyori Kaneko, Kentaro Kosaka, Daisuke Sawada, Aki Takada-Watanabe, Takuya Minamizuka, Yusuke Baba, Masaya Koshizaka, Akira Shimamoto, Yasuo Ouchi, Atsushi Iwama, Yusuke Endo, Naoya Takayama, Koji Eto, Yoshiro Maezawa, Koutaro Yokote

Distinct gene expression dynamics in developing and regenerating limbs
Chiara Sinigaglia, Alba Almazan, Marie Semon, Benjamin Gillet, Sandrine Hughes, Eric Edsinger, Michalis Averof, Mathilde Paris

Single cell chronoatlas of regenerating mouse livers reveals early Kupffer cell proliferation
Daniel Sánchez-Taltavull, Tess Brodie, Joel Zindel, Noëlle Dommann, Bas G.J. Surewaard, Adrian Keogh, Nicolas Mélin, Isabel Büchi, Riccardo Tombolini, Paul Kubes, Daniel Candinas, Guido Beldi, Deborah Stroka

Vestibular and auditory hair cell regeneration following targeted ablation of hair cells with diphtheria toxin in zebrafish
Erin Jimenez, Claire C. Slevin, Luis Colón-Cruz, Shawn M. Burgess

Notch signaling via Hey1 and Id2b regulates Müller glia’s regenerative response to retinal injury
Aresh Sahu, Sulochana Devi, Jonathan Jui, Daniel Goldman

Anal skin-like epithelium mediates colonic wound healing
Cambrian Y. Liu, Nandini Girish, Marie L. Gomez, Philip E. Dubé, M. Kay Washington, Benjamin D. Simons, D. Brent Polk

mTOR activity is essential for retinal pigment epithelium regeneration in zebrafish
Fangfang Lu, Lyndsay L. Leach, Jeffrey M. Gross

Potential therapy for progressive vision loss due to PCDH15-associated Usher Syndrome developed in an orthologous Usher mouse
Saumil Sethna, Wadih M. Zein, Sehar Riaz, Arnaud P. J. Giese, Julie M. Schultz, Todd Duncan, Robert B. Hufnagel, Carmen C. Brewer, Andrew J. Griffith, T. Michael Redmond, Saima Riazuddin, Thomas B. Friedman, Zubair M. Ahmed

A functional network signature in the developing cerebellum: evidence from a preclinical model of autism
María Berenice Soria-Ortiz, Atáulfo Martínez Torres, Daniel Reyes-Haro

Pharmacological inhibition of the VCP/proteasome axis rescues photoreceptor degeneration in RHOP23H rat retinal explants
Merve Sen, Oksana Kutsyr, Bowen Cao, Sylvia Bolz, Blanca Arango-Gonzalez, Marius Ueffing

Dissecting the molecular basis of human interneuron migration in forebrain assembloids from Timothy syndrome
Fikri Birey, Min-Yin Li, Aaron Gordon, Mayuri Thete, Alfredo M Valencia, Omer Revah, Anca M Pasca, Daniel H Geschwind, Sergiu P Pasca

Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord reproducibly models early events in ERK-mediated tumorigenesis
Axelle Wilmerding, Lauranne Bouteille, Nathalie Caruso, Ghislain Bidaut, Heather Etchevers, Yacine Graba, Marie-Claire Delfini

Mutations in SIX1 associated with Branchio-oto-renal Syndrome (BOR) differentially affect otic expression of putative target genes
Tanya Mehdizadeh, Himani Datta Majumdar, Sarah Ahsan, Andre Tavares, Sally A. Moody

Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers Danlos syndrome
Anne Legrand, Charline Guery, Julie Faugeroux, Erika Fontaine, Carole Beugnon, Amélie Gianfermi, Irmine Loisel-Ferreira, Marie-Christine Verpont, Salma Adham, Tristan Mirault, Juliette Hadchouel, Xavier Jeunemaitre

Maternal hyperglycemia impedes second heart field-derived cardiomyocyte differentiation to elevate the risk of congenital heart defects
Sathiyanarayanan Manivannan, Corrin Mansfield, Xinmin Zhang, Karthik M. Kodigepalli, Uddalak Majumdar, Vidu Garg, Madhumita Basu

Analysis of CHD-7 defective dauer nematodes implicates collagen misregulation in CHARGE syndrome features
Diego M. Jofré, Dane K. Hoffman, Ailen S. Cervino, McKenzie Grundy, Sijung Yun, Francis RG. Amrit, Donna B. Stolz, Esteban Salvatore, Fabiana A. Rossi, Arjumand Ghazi, M. Cecilia Cirio, Judith L. Yanowitz, Daniel Hochbaum

Identifying developing interneurons as a potential target for multiple genetic autism risk factors in human and rodent forebrain
Yifei Yang, Sam A. Booker, James M. Clegg, Idoia Quintana Urzainqui, Anna Sumera, Zrinko Kozic, Owen Dando, Sandra Martin Lorenzo, Yann Herault, Peter C. Kind, David J. Price, Thomas Pratt

BRN2 and PTN unveil multiple neurodevelopmental mechanisms in Schizophrenia patient-derived cerebral organoids
Michael Notaras, Aiman Lodhi, Friederike Dundar, Paul Collier, Nicole Sayles, Hagen Tilgner, David Greening, Dilek Colak

Inter- and intrapopulational heterogeneity of characteristic markers in adult human neural crest-derived stem cells
Beatrice A. Windmöller, Anna L. Höving, Johannes F.W. Greiner

PpRPK2 modulates auxin homeostasis and transport to specify stem cell identity and plant shape in the moss Physcomitrella
Zoe Nemec Venza, Connor Madden, Amy Stewart, Wei Liu, Ondřej Novák, Aleš Pěnčík, Andrew C. Cuming, Yasuko Kamisugi, C. Jill Harrison

Fetal-like reversion in the regenerating intestine is regulated by mesenchymal Asporin
Sharif Iqbal, Simon Andersson, Ernesta Nestaite, Nalle Pentinmikko, Ashish Kumar, Daniel Borshagovski, Anna Webb, Tuure Saarinen, Anne Juuti, Alessandro Ori, Markku Varjosalo, Kirsi H. Pietiläinen, Kim B. Jensen, Menno Oudhoff, Pekka Katajisto

A single-cell atlas of de novo β-cell regeneration reveals the contribution of hybrid β/δ cells to diabetes recovery in zebrafish
Sumeet Pal Singh, Prateek Chawla, Alisa Hnatiuk, Margrit Kamel, Luis Delgadillo Silva, Bastiaan Spanjard, Sema Elif Eski, Sharan Janjuha, Pedro Olivares, Oezge Kayisoglu, Fabian Rost, Juliane Bläsche, Annekathrin Kränkel, Andreas Petzold, Thomas Kurth, Susanne Reinhardt, Jan Philipp Junker, Nikolay Ninov

Modular, Cascade-like Transcriptional Program of Regeneration in Stentor
Pranidhi Sood, Athena Lin, Rebecca McGillivary, Wallace F. Marshall

A multimodal iPSC platform for cystic fibrosis drug testing
Andrew Berical, Rhianna E. Lee, Junjie Lu, Mary Lou Beermann, Jake A. LeSeur, Aditya Mithal, Dylan Thomas, Nicole Ranallo, Megan Peasley, Alex Stuffer, Jan Harrington, Kevin Coote, Killian Hurley, Paul McNally, Gustavo Mostovslavsky, John Mahoney, Scott H. Randell, Finn J. Hawkins

Dystonia-specific mutations in THAP1 alter transcription of genes associated with neurodevelopment and myelin
Aloysius Domingo, Rachita Yadav, Shivangi Shah, William T. Hendriks, Serkan Erdin, Dadi Gao, Kathryn O’Keefe, Benjamin Currall, James F. Gusella, Nutan Sharma, Laurie J. Ozelius, Michelle E. Ehrlich, Michael E. Talkowski, D. Cristopher Bragg

Inhibition of N-myristoyltransferase Promotes Naive Pluripotency in Mouse and Human Pluripotent Stem Cells
Junko Yoshida, Hitomi Watanabe, Kaori Yamauchi, Takumi Nishikubo, Ayako Isotani, Satoshi Ohtsuka, Hitoshi Niwa, Hidenori Akutsu, Akihiro Umezawa, Hirofumi Suemori, Yasuhiro Takashima, Gen Kondoh, Junji Takeda, Kyoji Horie

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

Stem cell-free therapy for glaucoma to preserve vision
Ajay Kumar, Xiong Siqi, Minwen Zhou, Wen Chen, Enzhi Yang, Andrew Price, Liang Le, Ying Zhang, Laurence Florens, Michael Washburn, Akshay Kumar, Yunshu Li, Yi Xu, Kira Lathrop, Katherine Davoli, Yuanyuan Chen, Joel S. Schuman, Ting Xie, Yiqin Du

Tfap2b specifies an embryonic melanocyte stem cell population that retains adult multi-fate potential
Alessandro Brombin, Daniel J. Simpson, Jana Travnickova, Hannah R. Brunsdon, Zhiqiang Zeng, Yuting Lu, Tamir Chandra, E. Elizabeth Patton

Single-cell RNA sequencing-based characterization of resident lung mesenchymal stromal cells in bronchopulmonary dysplasia
I. Mižíková, F. Lesage, C. Cyr-Depauw, D. P. Cook, M. Hurskainen, S.M. Hänninen, A. Vadivel, P. Bardin, S. Zhong, O. Carpen, B. C. Vanderhyden, B. Thébaud

Human iPSC-derived cerebral organoids model features of Leigh Syndrome and reveal abnormal corticogenesis
Alejandra I. Romero-Morales, Gabriella L. Robertson, Anuj Rastogi, Megan L. Rasmussen, Hoor Temuri, Gregory Scott McElroy, Ram Prosad Chakrabarty, Lawrence Hsu, Paula M. Almonacid, Bryan A. Millis, Navdeep S. Chandel, Jean-Philippe Cartailler, Vivian Gama

Zebrafish pigment cells develop directly from persistent highly multipotent progenitors
Masataka Nikaido, Tatiana Subkhankulova, Leonid A. Uroshlev, Artem J. Kasianov, Karen Camargo Sosa, Gemma Bavister, Xueyan Yang, Frederico S. L. M. Rodrigues, Thomas J. Carney, Hartmut Schwetlick, Jonathan H.P. Dawes, Andrea Rocco, Vsevelod Makeev, Robert N. Kelsh

Basal neural stem cells drive postnatal neurogenesis whereas apical stem cells act as proliferation gatekeepers by regulating notch activation in the postnatal ventricular-subventricular zone
Katja Baur, Yomn Abdullah, Claudia Mandl, Gabriele Hoelzl-Wenig, Yan Shi, Udo Schmidt-Edelkraut, Priti Khatri, Francesca Ciccolini

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

Single-cell transcriptome analysis of embryonic and adult endothelial cells allows to rank the hemogenic potential of post-natal endothelium
Artem Adamov, Yasmin Natalia Serina Secanechia, Christophe Lancrin

Control of Arabidopsis shoot stem cell homeostasis by two antagonistic CLE peptide signalling pathways
Jenia Schlegel, Grégoire Denay, Karine Gustavo Pinto, Yvonne Stahl, Julia Schmid, Patrick Blümke, Rüdiger Simon

Skeletal dysplasia-causing TRPV4 mutations suppress the hypertrophic differentiation of human iPSC-derived chondrocytes
Amanda R. Dicks, Grigory I. Maksaev, Zainab Harissa, Alireza Savadipour, Ruhang Tang, Nancy Steward, Wolfgang Liedtke, Colin G. Nichols, Chia-Lung Wu, Farshid Guilak

ZFP541 is indispensable for pachytene progression by interacting with KCTD19 and activates meiotic gene expression in mouse spermatogenesis
Yushan Li, Ranran Meng, Shanze Li, Bowen Gu, Xiaotong Xu, Haihang Zhang, Tianyu Shao, Jiawen Wang, Yinghua Zhuang, Fengchao Wang

Generation of liver organoids from human induced pluripotent stem cells as liver fibrosis and steatosis models
Hoi Ying Tsang, Paulisally Hau Yi Lo, Kenneth Ka Ho Lee

Oncofetal protein CRIPTO regulates wound healing and fibrogenesis in regenerating liver and is associated with the initial stages of cardiac fibrosis
Sofia Karkampouna, Danny van der Helm, Bart van Hoek, Hein W Verspaget, Marie Jose TH Goumans, Minneke Coenraad, Boudewijn TH Kruithof, Marianna Kruithof-deJulio

Unbiased in vivo exploration of nuclear bodies-enhanced sumoylation reveals that PML orchestrates embryonic stem cell fate
Sarah Tessier, Omar Ferhi, Marie-Claude Geoffroy, Roman Gonzalez-Prieto, Antoine Canat, Samuel Quentin, Marika Pla, Michiko Niwa-Kawakita, Pierre Bercier, Domitille Rerolle, Pierre Therizols, Emmanuelle Fabre, Alfred C.O. Vertegaal, Hugues de The, Valerie Lallemand-Breitenbach

Distinct epicardial gene regulatory programmes drive development and regeneration of the zebrafish heart
Michael Weinberger, Filipa C. Simoes, Tatjana Sauka-Spengler, Paul R. Riley

Kidney organoids: A system to study human basement membrane assembly in health and disease
Mychel RPT Morais, Pinyuan Tian, Craig Lawless, Syed Murtuza-Baker, Louise Hopkinson, Steven Woods, Aleksandr Mironov, David A Long, Daniel Gale, Telma MT Zorn, Roy Zent, Rachel Lennon

Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of the matricellular protein Mindin
Krithika Badarinath, Binita Dam, Sunny Kataria, Ravindra K. Zirmire, Rakesh Dey, Randhir Singh, Tafheem A. Masudi, Janani Sambath, Prashanth Kumar, Akash Gulyani, You-Wen He, Sudhir Krishna, Colin Jamora

Glypican-6 deficiency causes dose-dependent conotruncal congenital heart malformations through abnormal remodelling of the endocardial cushions
Gennadiy Tenin, Alexander Crozier, Kathryn E. Hentges, Bernard Keavney

TLR4 regulation in human fetal membranes as an explicative mechanism of a pathological preterm case
Corinne Belville, Flora Ponelle-Chachuat, Marion Rouzaire, Christelle Gross, Bruno Pereira, Denis Gallot, Vincent Sapin, Loïc Blanchon

Cell-autonomous differentiation of human primed embryonic stem cells into trophoblastic syncytia through the nascent amnion-like cell state
Masatoshi Ohgushi, Mototsugu Eiraku

Intrinsic and extrinsic regulation of human fetal bone marrow haematopoiesis and perturbations in Down syndrome
Laura Jardine, Simone Webb, Issac Goh, Mariana Quiroga Londoño, Gary Reynolds, Michael Mather, Bayanne Olabi, Emily Stephenson, Rachel A. Botting, Dave Horsfall, Justin Engelbert, Daniel Maunder, Nicole Mende, Caitlin Murnane, Emma Dann, Jim McGrath, Hamish King, Iwo Kucinski, Rachel Queen, Christopher D Carey, Caroline Shrubsole, Elizabeth Poyner, Meghan Acres, Claire Jones, Thomas Ness, Rowan Coulthard, Natalina Elliott, Sorcha O’Byrne, Myriam L. R. Haltalli, John E Lawrence, Steven Lisgo, Petra Balogh, Kerstin B Meyer, Elena Prigmore, Kirsty Ambridge, Mika Sarkin Jain, Mirjana Efremova, Keir Pickard, Thomas Creasey, Jaume Bacardit, Deborah Henderson, Jonathan Coxhead, Andrew Filby, Rafiqul Hussain, David Dixon, David McDonald, Dorin-Mirel Popescu, Monika S. Kowalczyk, Bo Li, Orr Ashenberg, Marcin Tabaka, Danielle Dionne, Timothy L. Tickle, Michal Slyper, Orit Rozenblatt-Rosen, Aviv Regev, Sam Behjati, Elisa Laurenti, Nicola K. Wilson, Anindita Roy, Berthold Göttgens, Irene Roberts, Sarah A. Teichmann, Muzlifah Haniffa

Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates
Andrea Toth, Shelby Steinmeyer, Paranthaman Kannan, Jerilyn Gray, Courtney M. Jackson, Shibabrata Mukherjee, Martin Demmert, Joshua R. Sheak, Daniel Benson, Joe Kitzmiller, Joseph A. Wayman, Pietro Presicce, Christopher Cates, Rhea Rubin, Kashish Chetal, Yina Du, Yifei Miao, Mingxia Gu, Minzhe Guo, Vladimir V. Kalinichenko, Suhas G. Kallapur, Emily R. Miraldi, Yan Xu, Daniel Swarr, Ian Lewkowich, Nathan Salomonis, Lisa Miller, Jennifer S. Sucre, Jeffrey A. Whitsett, Claire A. Chougnet, Alan H. Jobe, Hitesh Deshmukh, William J. Zacharias

Post-embryonic development and aging of the appendicular skeleton in Ambystoma mexicanum
Camilo Riquelme-Guzmán, Maritta Schuez, Alexander Böhm, Dunja Knapp, Sandra Edwards-Jorquera, Alberto S. Ceccarelli, Osvaldo Chara, Martina Rauner, Tatiana Sandoval-Guzmán

| Plant development

Populus ERF85 balances xylem cell expansion and secondary cell wall formation in hybrid aspen
Carolin Seyfferth, Bernard A Wessels, Jorma Vahala, Jaakko Kangasjarvi, Nicolas Delhomme, Torgeir R Hvidsten, Hannele Tuominen, Judith Felten

B1L regulates lateral root development by exocytic vesicular trafficking-mediated polar auxin transport in Arabidopsis
Gang Yang, Bi-xia Chen, Tao Chen, Jia-hui Chen, Rui Sun, Cong-cong Liu, Jiao Jia, Xiu-le Yue, Li-zhe An, Hua Zhang

Spindle position dictates division site during asymmetric cell division in moss
Elena Kozgunova, Mari W. Yoshida, Ralf Reski, Gohta Goshima

Maize Brittle Stalk2-Like3, encoding a COBRA protein, functions in cell wall formation and carbohydrate partitioning
Benjamin T. Julius, Tyler J. McCubbin, Rachel A. Mertz, Nick Baert, Jan Knoblauch, DeAna G. Grant, Kyle Conner, Saadia Bihmidine, Paul Chomet, Ruth Wagner, Jeff Woessner, Karen Grote, Jeanette Peevers, Thomas L. Slewinski, Maureen C. McCann, Nicholas C. Carpita, Michael Knoblauch, David M. Braun

Protein turnover in the developing Triticum aestivum grain
Hui Cao, Owen Duncan, A. Harvey Millar

Suberin plasticity to developmental and exogenous cues is regulated by a set of MYB transcription factors
Vinay Shukla, Jian-Pu Han, Fabienne Cléard, Linnka Lefebvre- Legendre, Kay Gully, Paulina Flis, Alice Berhin, Tonni Grube Andersen, David E Salt, Christiane Nawrath, Marie Barberon

Endogenous RNA editing of a nuclear gene BOSS triggers flowering in tomato
Wenqian Wang, Jie Ye, Chuying Yu, Qingmin Xie, Xin Wang, Huiyang Yu, Jianwen Song, Changxing Li, Long Cui, Heyou Han, Changxian Yang, Hanxia Li, Yongen Lu, Taotao Wang, Yuyang Zhang, Junhong Zhang, Bo Ouyang, Zhibiao Ye

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

Chromatin enrichment for Proteomics in Plants (ChEP-P) implicates the histone reader ALFIN-LIKE 6 in jasmonate signalling
Isabel Cristina Vélez-Bermúdez, Wolfgang Schmidt

Timing of meristem initiation and maintenance determines the morphology of fern gametophytes
Xiao Wu, An Yan, Scott McAdam, Jo Ann Banks, Shaoling Zhang, Yun Zhou

The Genetic Architecture of Strawberry Yield and Fruit Quality Traits
Helen M. Cockerton, Amanda Karlström, Abigail W. Johnson, Bo Li, Eleftheria Stavridou, Katie J. Hopson, Adam B. Whitehouse, Richard J. Harrison

The REF6-dependent H3K27 demethylation establishes transcriptional competence to promote germination in Arabidopsis
Jie Pan, Huairen Zhang, Zhenping Zhan, Ting Zhao, Danhua Jiang

Regulation of suberin biosynthesis and Casparian strip development in the root endodermis by two plant auxins
Sam David Cook, Seisuke Kimura, Qi Wu, Rochus Benni Franke, Takehiro Kamiya, Hiroyuki Kasahara

Estimation of cell cycle kinetics in higher plant root meristem links organ position with cellular fate and chromatin structure
Taras Pasternak, Stefan Kircher, Klaus Palme

The VIL gene CRAWLING ELEPHANT controls maturation and differentiation in tomato via polycomb silencing
Ido Shwartz, Chen Yahav, Neta Kovetz, Alon Israeli, Maya Bar, Matan Levy, Katherine L. Duval, José M. Jiménez-Gómez, Roger B. Deal, Naomi Ori

A quantitative gibberellin signalling biosensor reveals a role for gibberellins in internode specification at the shoot apical meristem
Bihai Shi, Amelia Felipo-Benavent, Guillaume Cerutti, Carlos Galvan-Ampudia, Lucas Jilli, Geraldine Brunoud, Jérome Mutterer, Lali Sakvarelidze-Achard, Jean-Michel Davière, Alejandro Navarro-Galiano, Ankit Walia, Shani Lazary, Jonathan Legrand, Roy Weinstein, Alexander M. Jones, Salomé Prat, Patrick Achard, Teva Vernoux

Adaptive reprogramming during early seed germination requires temporarily enhanced fermentation – a critical role for alternative oxidase (AOX) regulation that concerns also microbiota effectiveness
Bharadwaj Revuru, Carlos Noceda, Mohanapriya Gunasekaran, Sarma Rajeev Kumar, Karine Leitão Lima Thiers, José Hélio Costa, Elisete Santos Macedo, Aprajita Kumari, Kapuganti Jagadis Gupta, Shivani Srivastava, Alok Adholeya, Manuela Oliveira, Isabel Velada, Debabrata Sircar, Ramalingam Sathishkumar, Birgit Arnholdt-Schmitt

Ovule siRNAs methylate and silence protein-coding genes in trans
Diane Burgess, Hiu Tung Chow, Jeffrey W. Grover, Michael Freeling, Rebecca A. Mosher

SlKIX8 and SlKIX9 are negative regulators of leaf and fruit growth in tomato
Gwen Swinnen, Jean-Philippe Mauxion, Alexandra Baekelandt, Rebecca De Clercq, Jan Van Doorsselaere, Dirk Inzé, Nathalie Gonzalez, Alain Goossens, Laurens Pauwels

Shade-induced WRKY transcription factors restrict root growth during the shade avoidance response
Daniele Rosado, Amanda Ackermann, Olya Spassibojko, Magdalena Rossi, Ullas V. Pedmale

The U1 snRNP component RBP45d regulates temperature-responsive flowering in Arabidopsis thaliana
Ping Chang, Hsin-Yu Hsieh, Shih-Long Tu

INDEHISCENT regulates explosive seed dispersal
Anahit Galstyan, Penny Sarchet, Rafael Campos-Martin, Milad Adibi, Lachezar A. Nikolov, Miguel Pérez Antón, Léa Rambaud-Lavigne, Xiangchao Gan, Angela Hay

Seed morphological traits as a tool to quantify variation maintained in ex situ collections: a case study in Pinus torreyana (Parry)
Lionel N Di Santo, Monica Polgar, Storm Nies, Paul Hodgkiss, Courtney A Canning, Jessica W Wright, Jill A Hamilton

DNA METHYLTRANSFERASE 3 (MET3) is regulated by Polycomb Group complex during Arabidopsis endosperm development
Louis Tirot, Pauline E. Jullien

Developmental Effects on Relative Use of PEPCK and NADP-ME Pathways of C4 Photosynthesis in Maize
Jennifer J. Arp, Shrikaar Kambhampati, Kevin L. Chu, Somnath Koley, Lauren M. Jenkins, Todd C. Mockler, Doug K. Allen

GTL1 is required for a robust root hair growth response to avoid nutrient overloading
Michitaro Shibata, David S. Favero, Ryu Takebayashi, Ayako Kawamura, Bart Rymen, Yoichiroh Hosokawa, Keiko Sugimoto

Transcriptional activation of auxin biosynthesis drives developmental reprogramming of differentiated cells
Yuki Sakamoto, Ayako Kawamura, Takamasa Suzuki, Shoji Segami, Masayoshi Maeshima, Stefanie Polyn, Lieven De Veylder, Keiko Sugimoto

Genetic basis and dual adaptive role of floral pigmentation in sunflowers
Marco Todesco, Natalia Bercovich, Amy Kim, Ivana Imerovski, Gregory L. Owens, Óscar Dorado Ruiz, Srinidhi V. Holalu, Lufiani L. Madilao, Mojtaba Jahani, Jean-Sébastien Légaré, Benjamin K. Blackman, Loren H. Rieseberg

Arabidopsis stomatal polarity protein BASL mediates distinct processes before and after cell division to coordinate cell size and fate asymmetries
Yan Gong, Julien Alassimone, Andrew Muroyama, Gabriel Amador, Rachel Varnau, Ao Liu, Dominique C. Bergmann

Arabidopsis ABIG1 Functions in Laminar Growth and Polarity Formation through Regulation by REVOLUTA and KANADI
Jesus Preciado, Kevin Begcy, Tie Liu

3D reconstruction identifies loci linked to variation in angle of individual sorghum leaves
Michael C. Tross, Mathieu Gaillard, Mackenzie Zweiner, Chenyong Miao, Bosheng Li, Bedrich Benes, James C. Schnable

Members of the ELMOD protein family specify formation of distinct aperture domains on the Arabidopsis pollen surface
Yuan Zhou, Prativa Amom, Sarah H. Reeder, Byung Ha Lee, Adam Helton, Anna A. Dobritsa

Ureides are similarly accumulated in response to UV-C irradiation and wound but differently remobilized during recovery in Arabidopsis leaves.
Aigerim Soltabayeva, Aizat Bekturova, Assylay Kurmanbayeva, Dinara Oshanova, Zhadyrassyn Nurbekova, Sudhakar Srivastava, Dominic Standing, Moshe Sagi

| Evo-devo

Evolution of the nitric oxide synthase family in vertebrates and novel insights in gill development
Giovanni Annona, Iori Sato, Juan Pascual-Anaya, Ingo Braasch, Randal Voss, Jan Stundl, Vladimir Soukup, Sihigeru Kuratani, John Postlethwait, Salvatore D’Aniello

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

Single-nucleus transcriptomes reveal functional and evolutionary properties of cell types in the Drosophila accessory gland
Alex C. Majane, Julie M. Cridland, David J. Begun

Evolutionary transition of doublesex regulation in termites and cockroaches: from sex-specific splicing to male-specific transcription
Satoshi Miyazaki, Kokuto Fujiwara, Keima Kai, Yudai Masuoka, Hiroki Gotoh, Teruyuki Niimi, Yoshinobu Hayashi, Shuji Shigenobu, Kiyoto Maekawa

Complete metamorphosis and microbiota turnover in insects
Christin Manthey, Paul R Johsnton, Jens Rolff

Facultative release from developmental constraints through polyphenism promotes adaptively flexible maturation
Flor T. Rhebergen, Isabel M. Smallegange

A large disordered region confers a wide spanning volume to vertebrate Suppressor of Fused as shown in a trans-species solution study
Staëlle Makamte, Amira Jabrani, Annick Paquelin, Anne Plessis, Mathieu Sanial, Aurélien Thureau, Olga Rudenko, Francesco Oteri, Marc Baaden, Valérie Biou

Developmental plasticity in male courtship in Bicyclus anynana butterflies is driven by hormone regulation of the yellow gene
Heidi Connahs, Eunice Jingmei Tan, Yi Ting Ter, Emilie Dion, Yuji Matsuoka, Ashley Bear, Antónia Monteiro

Convergent adaptation and ecological speciation result from unique genomic mechanisms in sympatric extremophile fishes
Ryan Greenway, Anthony P. Brown, Henry Camarillo, Cassandra Delich, Kerry L. McGowan, Joel Nelson, Lenin Arias-Rodriguez, Joanna L. Kelley, Michael Tobler

Behavioural adaptations in egg laying ancestors facilitate evolutionary transitions to live birth
Amanda K. Pettersen, Nathalie Feiner, Daniel W.A. Noble, Geoffrey M. While, Charlie K. Cornwallis, Tobias Uller

Functional divergence of the bag of marbles gene in the Drosophila melanogaster species group
Jaclyn E. Bubnell, Cynthia K.S. Ulbing, Paula Fernandez-Begne, Charles F. Aquadro

Adaptive shifts underlie the divergence in wing morphology in bombycoid moths
Brett R. Aiello, Milton Tan, Usama Bin Sikandar, Alexis J. Alvey, Burhanuddin Bhinderwala, Katalina C. Kimball, Jesse R. Barber, Chris A. Hamilton, Akito Y. Kawahara, Simon Sponberg

An evolutionarily conserved odontode gene regulatory network underlies head armor formation in suckermouth armored catfish
Shunsuke Mori, Tetsuya Nakamura

Evolution of lbx spinal cord expression and function
José Luis Juárez-Morales, Frida Weierud, Samantha J. England, Celia Demby, Nicole Santos, Ginny Grieb, Sylvie Mazan, Katharine E. Lewis

Evolution of Drosophila buzzatii wings: Modular genetic organization, sex-biased integrative selection and intralocus sexual conflict
PP Iglesias, FA Machado, S Llanes, E Hasson, EM Soto

Sex-Specific Plasticity Explains Genetic Variation in Sexual Size Dimorphism in Drosophila
Isabelle M Vea, Austin Wilcox, W. Anthony Frankino, Alexander W Shingleton

Cell Biology

A mechano-osmotic feedback couples cell volume to the rate of cell deformation
Larisa Venkova, Amit Singh Vishen, Sergio Lembo, Nishit Srivastava, Baptiste Duchamp, Artur Ruppel, Stéphane Vassilopoulos, Alexandre Deslys, Juan Manuel Garcia Arcos, Alba Diz-Muñoz, Martial Balland, Jean-François Joanny, Damien Cuvelier, Pierre Sens, Matthieu Piel

Volume growth in animal cells is cell cycle dependent and shows additive fluctuations
Clotilde Cadart, Matthieu Piel, Marco Cosentino Lagomarsino

A particle size threshold governs diffusion and segregation of PAR-3 during cell polarization
Yiran Chang, Daniel J. Dickinson

KIF18B is a cell-type specific regulator of spindle orientation in the epidermis
Rebecca S. Moreci, Terry Lechler

A ciliopathy complex builds distal appendages to initiate ciliogenesis
Dhivya Kumar, Addison Rains, Vicente Herranz-Pérez, Quanlong Lu, Xiaoyu Shi, Danielle L. Swaney, Erica Stevenson, Nevan J. Krogan, Bo Huang, Christopher Westlake, Jose Manuel Garcia-Verdugo, Bradley Yoder, Jeremy F. Reiter

Mouse oocytes do not contain a Balbiani body
Laasya Dhandapani, Marion C. Salzer, Juan M. Duran, Gabriele Zaffagnini, Cristian De Guirior, Maria Angeles Martínez-Zamora, Elvan Böke

SLC1A5 provides glutamine and asparagine necessary for bone development in mice
Deepika Sharma, Yilin Yu, Leyao Shen, Guo-Fang Zhang, Courtney Karner

The Transcriptional Co-Activator Taz Contributes to the Differentiation of a Salivary Gland Epithelial Cell Line Towards a Myoepithelial Phenotype
Renee F. Thiemann, Scott Varney, Nicholas Moskwa, John Lamar, Melinda Larsen, Susan E. LaFlamme

Anoikis resistance in mammary epithelial cells is mediated by semaphorin 7a
Taylor R. Rutherford, Alan M Elder, Traci R. Lyons

A steroid hormone regulates growth in response to oxygen availability
George P. Kapali, Viviane Callier, Hailey Broeker, Parth Tank, Samuel J.L. Gascoigne, Jon F Harrison, Alexander W. Shingleton

Modelling

Cell types and ontologies of the Human Cell Atlas

David Osumi-Sutherland, Chuan Xu, Maria Keays, Peter V. Kharchenko, Aviv Regev, Ed Lein, Sarah A. Teichmann

Computational modelling of cell motility modes emerging from cell-matrix adhesion dynamics
Leonie van Steijn, Clément Sire, Loïc Dupré, Guy Theraulaz, Roeland M.H. Merks

A landscape model for cell fate decisions during mesoendoderm differentiation in C. elegans based on Wnt dynamics
Shyr-Shea Chang, Zhirong Bao, Eric D. Siggia

The extra-embryonic space is a geometric constraint regulating cell arrangement in nematodes
Sungrim Seirin-Lee, Akatsuki Kimura

From heterogeneous datasets to predictive models of embryonic development
Sayantan Dutta, Aleena L. Patel, Shannon E. Keenan, Stanislav Y. Shvartsman

Graph-based machine learning reveals rules of spatiotemporal cell interactions in tissues
Takaki Yamamoto, Katie Cockburn, Valentina Greco, Kyogo Kawaguchi

Blastocoel morphogenesis: a biophysics perspective

Mathieu Le-Verge-Serandour, Hervé Turlier

Disorder in cellular packing can alter proliferation dynamics to regulate growth

Chandrashekar Kuyyamudi, Shakti N. Menon, Fernando Casares, Sitabhra Sinha

Tools & Resources

hei-tag: a highly efficient tag to boost targeted genome editing
Thomas Thumberger, Tinatini Tavhelidse, Jose Arturo Gutierrez-Triana, Rebekka Medert, Alex Cornean, Bettina Welz, Marc Freichel, Joachim Wittbrodt

NanoDam identifies novel temporal transcription factors conserved between the Drosophila central brain and visual system
Jocelyn L.Y. Tang, Anna E. Hakes, Robert Krautz, Takumi Suzuki, Esteban G. Contreras, Paul M. Fox, Andrea H. Brand

Toward a More Accurate 3D Atlas of C. elegans Neurons
Michael Skuhersky, Tailin Wu, Eviatar Yemini, Edward Boyden, Max Tegmark

Genome editing in animals with minimal PAM CRISPR-Cas9 enzymes
Jeremy Vicencio, Carlos Sánchez-Bolaños, Ismael Moreno-Sánchez, David Brena, Dmytro Kukhtar, Miguel Ruiz-López, Mariona Cots-Ponjoan, Charles E. Vejnar, Alejandro Rubio, Natalia Rodrigo Melero, Carlo Carolis, Antonio J. Pérez-Pulido, Antonio J. Giráldez, Benjamin P. Kleinstiver, Julián Cerón, Miguel A. Moreno-Mateos

A CRISPR toolbox for generating intersectional genetic mice for functional, molecular, and anatomical circuit mapping
Savannah J. Lusk, Andrew McKinney, Patrick J. Hunt, Paul G. Fahey, Jay Patel, Jenny J. Sun, Vena K. Martinez, Ping Jun Zhu, Jeremy R. Egbert, Xiaolong Jiang, Benjamin R. Arenkiel, Andreas S. Tolias, Mauro Costa-Mattioli, Russell S. Ray

Extremely bright, near-IR emitting spontaneously blinking fluorophores enable ratiometric multicolor nanoscopy in live cells
Jonathan Tyson, Kevin Hu, Shuai Zheng, Phylicia Kidd, Neville Dadina, Ling Chu, Derek Toomre, Joerg Bewersdorf, Alanna Schepartz

CeLINC, a fluorescence-based protein-protein interaction assay in C. elegans
Jason R Kroll, Sanne Remmelzwaal, Mike Boxem

Anatomical Structures, Cell Types, and Biomarkers Tables Plus 3D Reference Organs in Support of a Human Reference Atlas
Katy Börner, Sarah A. Teichmann, Ellen M. Quardokus, James Gee, Kristen Browne, David Osumi-Sutherland, Bruce W. Herr II, Andreas Bueckle, Hrishikesh Paul, Muzlifah A. Haniffa, Laura Jardine, Amy Bernard, Song-Lin Ding, Jeremy A. Miller, Shin Lin, Marc Halushka, Avinash Boppana, Teri A. Longacre, John Hickey, Yiing Lin, M. Todd Valerius, Yongqun He, Gloria Pryhuber, Xin Sun, Marda Jorgensen, Andrea J. Radtke, Clive Wasserfall, Fiona Ginty, Jonhan Ho, Joel Sunshine, Rebecca T. Beuschel, Maigan Brusko, Sujin Lee, Rajeev Malhotra, Sanjay Jain, Griffin Weber

Fast 3D Clear: A Fast, Aqueous-Based, Reversible Three-Day Tissue Clearing Method for Adult and Embryonic Mouse Brain and Whole Body
Stylianos Kosmidis, Adrian Negrean, Alex Dranovsky, Attila Losonczy, Eric R. Kandel

The developmental transcriptome of Parhyale hawaiensis: microRNAs and mRNAs show different expression dynamics during the maternal-zygotic transition
Llilians Calvo, Maria Birgaoanu, Tom Pettini, Matthew Ronshaugen, Sam Griffiths-Jones

Tissue-specific modification of cellular bioelectrical activities using the chemogenetic tool, DREADD, in zebrafish
Martin R. Silic, GuangJun Zhang

Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Zidong Zhang, Michel Zamojski, Gregory R. Smith, Thea L. Willis, Val Yianni, Natalia Mendelev, Hanna Pincas, Nitish Seenarine, Mary Anne S. Amper, Mital Vasoya, Venugopalan D. Nair, Judith L. Turgeon, Daniel J. Bernard, Olga G. Troyanskaya, Cynthia L. Andoniadou, Stuart C. Sealfon, Frederique Ruf-Zamojski

Zebrafish Cre/lox regulated UFlip alleles generated by CRISPR/Cas targeted integration provide cell-type specific conditional gene inactivation
Maira P. Almeida, Sekhar Kambakam, Fang Liu, Zhitao Ming, Jordan M. Welker, Wesley A. Wierson, Laura E. Schultz-Rogers, Stephen C. Ekker, Karl J. Clark, Jeffrey J. Essner, Maura McGrail

A highly efficient reporter system for identifying and characterizing in vitro expanded hematopoietic stem cells
James L.C. Che, Daniel Bode, Iwo Kucinski, Alyssa H. Cull, Fiona Bain, Melania Barile, Grace Boyd, Miriam Belmonte, Maria Jassinskaja, Juan Rubio-Lara, Mairi S. Shepherd, Anna Clay, Adam C. Wilkinson, Hiromitsu Nakauchi, Satoshi Yamazaki, Berthold Göttgens, David G. Kent

Forward genetics combined with unsupervised classifications identified zebrafish mutants affecting biliary system formation
Divya Jyoti Singh, Kathryn M. Tuscano, Karen L. Ortega, Manali Dimri, Kevin Tae, William Lee, Muslim A. Muslim, Jay L. Liu, Lain X. Pierce, Allyson McClendon, Gregory Naegele, Isabel Gibson, Jodi Livesay, Takuya F. Sakaguchi

Research practice & education

Building Back More Equitable STEM Education: Teach Science by Engaging Students in Doing Science
Sarah C R Elgin, Shan Hays, Vida Mingo, Christopher D Shaffer, Jason Williams

TeamTree analysis: a new approach to evaluate scientific production
Frank W. Pfrieger

I, We, and They: A Linguistic and Narrative Exploration of the Authorship Process
Abigail Konopasky, Bridget C O’Brien, Anthony R Artino Jr., Erik W Driessen, Christopher J Watling, Lauren A Maggio

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This interview, the 94th in our series, was published in Development earlier this year. 

A dynamic pattern of histone methylation and demethylation controls gene expression during development, with some processes such as formation of the zygote involving large-scale reprogramming of methylation states. A new paper in Development investigates how inherited histone methylation regulates developmental timing and the germline/soma distinction in Caenorhabditis elegans. To hear more about the story we caught up with first author and postdoctoral researcher Brandon Carpenter, and his supervisor David Katz, Associate Professor in the Department of Cell Biology at Emory University School of Medicine in Atlanta, Georgia.

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

DK: As a graduate student, I worked with Dr Shirley Tilghman at Princeton on the regulation of genomic imprinting. We provided in vivo evidence for the first chromatin boundary formed by CTCF at the H19 locus in mouse. As a postdoc, I worked for Dr Bill Kelly at Emory University on the regulation of histone methylation in the germline of C. elegans. We provided the first evidence of a transgenerational phenotype (sterility) caused by the build-up of histone methylation, when the H3K4me1/2 demethylase Lsd1 is mutated. In my own lab at the Emory University School of Medicine, we have worked on both C. elegans and mouse model systems to study the mechanisms that regulate histone methylation and how inappropriately inherited histone methylation gives rise to phenotypes. We have also implicated LSD1 as a crucial molecule that may contribute to Alzheimer’s disease: our data suggest it is being inhibited by pathological aggregates in dementia patients. We are currently trying to develop a therapeutic intervention based on what we have learned about the function of LSD1 in the Alzheimer’s disease pathway.

Brandon – how did you come to work in David’s lab and what drives your research today?

BC: After obtaining my doctoral degree, I knew I wanted to continue studying development, and that I wanted to focus on a model system that would allow undergraduates to develop projects related to my research. As a graduate student, I fell in love with mentoring students and wanted to find opportunities to inspire students in the classroom as well as at the bench. Thus, my passion for mentoring and studying developmental biology led me to the Katz lab, where I could work with the beautiful model system, C. elegans, to study how epigenetic inheritance affects developmental cell fates.

At Emory University, I joined the Katz lab as a Fellowship In Research and Science Teaching (FIRST) Fellow (part of the National Institutes of Health-funded IRACDA programme) where, in parallel with my research, I was able to develop my teaching and mentorship skills. The most exciting part of joining the Katz lab was being able to bring my research into the classroom at Oglethorpe University, a nearby small liberal arts college. The Katz lab has a longstanding collaboration with Dr Karen Schmeichel from the biology department at Oglethorpe, integrating C. elegans experiments into the entire curriculum. As part of this, I was able to teach a semester-long Course-based Undergraduate Research Experience (CURE) based on the research I was conducting in the Katz lab. As part of this semester-long CURE, Oglethorpe students became inspired by the science we are doing in the Katz Lab and generated data for this manuscript. Jovan Brockett, an undergraduate student, is an author on this manuscript for research he did in the classroom! My passion for understanding how an organism develops from a single cell drives my research, and the feeling I get when I see my mentees succeed while studying these mechanisms provides the fuel that keeps me going.

How has your research been affected by the COVID-19 pandemic?

BC: For me, COVID-19 hit right as I was finishing the experiments for two of my postdoctoral projects. During the ∼2-3 month lab shut down I was able to stay productive by submitting and revising manuscripts, but being away from the lab made it hard to advance interesting new ideas. The thing I miss most about not being able to go into lab is my ability to bounce crazy ideas off my talented Katz lab colleagues.

Before your work, what was known about the role of inherited histone methylation in the germline/soma distinction?

BC, DK: This paper is really about two major lines of research coming together to create a new story. We had been working on how two histone modifying enzymes, the H3K4me1/2 demethylase LSD1 (SPR-5 in C. elegans) and the H3K9 methyltransferase MET-2 cooperate to reprogramme histone methylation at fertilization to prevent the inappropriate chromatin environment from being passed on from one generation to the next. We had found that a failure to reprogramme histone methylation in spr-5; met-2 double mutants causes a maternal effect developmental delay and sterility phenotype. We were interested in how the inappropriate inheritance of histone methylation causes the developmental delay. Dr Susan Strome, with some help from Dr Bill Kelly, had performed some beautiful work showing how maternal deposition of the H3K6 methyltransferase is required transgenerationally to help specify the germline in progeny. Brandon had noticed some similarities between the developmental delay that we were observing and some high temperature phenotypes that Susan Strome had shown and were continuing to be worked on by Dr Lisa Patrella in her own lab. As detailed below, Brandon was able to show that the MES-4 system and the SPR-5; MET-2 reprogramming mechanism antagonize one another. It is also important to note that several labs have identified somatic repression mechanisms that antagonize the MES-4 system. We are interested in seeing how these systems interface with SPR-5; MET-2 reprogramming, so stay tuned!

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

BC, DK: We had previously shown that SPR-5 and MET-2 act together to repress germline genes at fertilization. In this paper, we found that H3K36 methylation antagonizes this repression to prevent these germline genes from being completely shut down. Without inherited H3K36 methylation, the germline is not properly specified. In contrast, without SPR-5; MET-2 repression, H3K36 is inappropriately propagated to the soma, resulting in germline genes being inappropriately expressed there. The inappropriate expression of germline genes in the soma results in a developmental delay. Thus, neither SPR-5; MET-2 reprogramming nor the MES-4 germline inheritance system can properly function without each other. Instead SPR-5, MET-2 and MES-4 coordinately balance three difference histone modifications (H3K4, H3K9 and H3K36 methylation) to ensure that germline versus soma is properly specified.

Why do you think inappropriate somatic expression of germline genes causes developmental delay?

BC, DK: As discussed in the paper, we think that there are two possible mechanisms for how the ectopic expression of germline genes causes developmental delay in spr-5; met-2 mutants. One possibility is that transcription of the germline programme itself causes the developmental delay. For example, if germline transcription factors are competing with somatic transcription factors to turn on genes, it is possible that the mix of proteins generated is simply too confusing for the cell to commit to its proper cell fate. The alternative is that a part of the germline function interferes with somatic development; for example, the germline precursors undergo a cell cycle arrest. It is possible that the proteins involved in this germline cell cycle checkpoint slow the progression of somatic cells via cell cycle regulation. Consistent with this latter possibility, we show that spr-5; met-2 mutants can silence an extrachromosomal array in the soma. This function, which is normally confined to the germline, suggests that somatic tissues in spr-5; met-2 mutants make proteins that can perform some germline functions. Thus, it is possible that a germline function acting in the soma prevents somatic cells from quickly adopting their proper cell fate.

What relevance do your data have for human patients harbouring mutations in histone-modifying enzymes?

BC, DK: Recent genome sequencing has revealed that several neurodevelopmental disorders are caused by mutations in histone-modifying enzymes. These include mutations in: (1) the H3K36 methyltransferase Setd2, the H3K27 demethylase Kdm6a and the H3K4 methyltransferase Kmt2d, which cause Kabuki Syndrome; (2) the human orthologue of spr-5, LSD1, which causes a Kabuki-like Syndrome; and (3) the H3K36 methyltransferase Nsd1, which causes Sotos Syndrome. Similar to what we observed in spr-5; met-2 mutant progeny, many of the human patients with mutations in these histone-modifying enzymes suffer from global developmental delay. Based on our model, it is possible that the developmental delay in these patients may be caused by the failure to properly regulate histone methylation during essential developmental transitions. Consistent with this, we have recapitulated some phenotypes in a maternal hypomorphic mutant of Lsd1 in mice that are reminiscent of Kabuki Syndrome. We hope that by continuing to study how mutations in histone-modifying enzymes in C. elegans and mice give rise to developmental defects, we will shed light on the human diseases caused by defects in histone-modifying enzymes.

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

BC: As detailed above, I had made the observation that the developmental delay we were observing had some similarities to some high-temperature phenotypes that Susan Strome had shown and were continuing to be worked on by Lisa Patrella in her own lab. This raised the possibility of a connection between SPR-5; MET-2 reprogramming and the MES-4 inheritance system. The crucial test of this potential connection was to knock down mes-4 via RNAi and see if it rescued the developmental delay, and we were very excited to find that it did rescue it, and even more excited when our RNA-seq subsequently showed that MES-4 germline genes are expressed in the somatic tissues of spr-5; met-2 mutants. After this independent confirmation of the connection between the two systems, we were confident that we had figured it out.

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

BC: The most frustrating part of this project was trying to gather enough L1 larvae to perform the initial genomic experiments. When we first started the project, there were no strains available that could balance the spr-5 mutant allele. I had to genotype every single hermaphrodite parent! At one point, I thought I would never get enough larvae to perform the genomic experiments. But David saw on science Twitter that the Caenorhabditis Genetics Center (CGC), which houses C. elegans strains, was developing new balancer strains. I contacted them and was able to get the FX30208 tmC27 [unc-75(tmls1239)](I) balancer even before they made it available to the broader C. elegans community. By reporting back that it worked well, I was also able to give back to the C. elegans community.

What next for you after this paper?

BC: I am officially on the academic job market searching for a tenure-track position and developing exciting new projects of my own that stem from this paper. We have mounting evidence that mutations in highly conserved histone-modifying enzymes may give rise to developmental phenotypes in vertebrates that are similar to what we observe in C. elegans. I want to take advantage of C. elegans mutants that fail to properly inherit histone methylation to further investigate how inherited chromatin states affect complex developmental processes like cell-to-cell communication and cell migration. I am also interested in potentially introducing the human version of Lsd1 into C. elegans to humanize the worm so that I can generate mutations that have been found in the human LSD1 patients. This type of approach is on-going through the NIH-funded Undiagnosed Diseases Network (UDN).

Where will this story take the Katz lab?

DK: We believe that spr-5; met-2 double mutants provide an excellent model for understanding how cells respond to inappropriately inherited histone methylation. We are taking advantage of the invariant embryonic cell lineage in C. elegans by performing automated lineage tracing experiments in spr-5; met-2 mutants. This will enable us to understand cell by cell how inappropriately inherited histone methylation affects processes such as cell division timing, cell migration, programmed cell death, etc. We hope to combine this with single cell RNA-seq to ask how each cell responds transcriptionally to this inappropriately inherited histone methylation. So stay tuned.

Remarkably, trying to understand the regulation of histone methylation in the germline has also taken us into the Alzheimer’s disease field. While trying to understand whether SPR-5; MET-2 reprogramming is conserved in mice, we serendipitously discovered that LSD1 is continually required for the survival of hippocampus and cortex neurons. We are interested in the possibility that terminally differentiated cells continually employ histone-modifying enzymes, such as LSD1, to maintain their cell fate. In the meantime, we have gone on to provide evidence that LSD1 is inhibited by pathological aggregates of tau in mice and human Alzheimer’s disease patients. We believe that this inhibition is a crucial part of how pathological tau induces neurodegeneration. So, you never know where developmental biology will lead!

You never know where developmental biology will lead!

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

BC: I like to go hiking with my 5-year-old twin daughters, play golf, and find cool breweries who push the edge on brewing delicious stouts and IPAs!

DK: I enjoy soccer with my 13-year-old twins and co-host a popular Atlanta United podcast. I also co-founded a very small vineyard just outside Atlanta at a friend’s house, and we have just produced our first successful vintage of a Norton/Cabernet Sauvignon blend. But I am also happy to drink a local beer with my outstanding postdoc Brandon.

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In this episode of Genetics Unzipped, supported by the Institute of Genetics and Cancer at the University of Edinburgh, Kat Arney sits down with Professor Bob Hill to take a look at the story of our favourite gene (we’ve all got one, right?).

From six-toed cats to cyclops lambs – and, of course, it’s fabulous name – the Sonic Hedgehog gene has a fascinating history, as well as a whole bunch of interesting developmental biology behind it. 

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

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

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

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

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By Koichiro Uriu, Bo-Kai Liao, Andrew C. Oates and Luis G. Morelli

How local cell-cell communication can generate a global tissue pattern is one of the fundamental questions in developmental biology. Yet, studying this remains challenging, because developing tissues involve complexities such as cell rearrangement, heterogeneity along the body axis, and massive tissue shape changes. In our recent paper in eLife (Uriu, Liao et al. 2021), we addressed this question using the zebrafish segmentation clock as a model system. Our integration of experimental and theoretical approaches revealed that after desynchronization, the recovery of the iconic synchronized wave pattern in the segmentation clock is influenced by two distinct spatial and temporal scales. Firstly, there is the faster and local communication directly between the cells, and secondly, there is a slower and much longer-distance movement of the cells and the tissues in the embryo as the tissues change their overall shapes.

This work started about 10 years ago, when the four of us were all at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany. In fact, we all worked in the same research group, so local communication was relatively easy. This local discussion was triggered when one of us, Bo-Kai Liao, noticed an unusual pattern of disrupted body segments in zebrafish embryos as they attempted to re-synchronize their cellular clocks after perturbation. The thing that struck us was that the pattern really couldn’t be explained by the current models of re-synchronization.

We are sure you all recognize the situation: “Hang on a minute, that should not be happening…” and you just know you are going to find out something cool. Well, in this case, the journey from initial observation to an explanation would take us a decade, during which time all of us moved from the MPI-CBG. We each moved country at least once, and we changed jobs and titles and had families and even got some grey hair. The scientific story mirrored the personal: how local communication is affected by long-distance movements. To understand this story better, we need to go back to the beginning and start with the biology.  

The precursors of the body segments of vertebrates, called somites, are formed rhythmically during embryonic development. Each segment buds off from the unsegmented tissue, presomitic mesoderm (PSM) one by one. The rhythm of segment formation is determined by an oscillatory spatial pattern of gene expression in the PSM and tailbud, termed the segmentation clock. In these tissues, the peaks of gene expression travel across the anterior-posterior axis. Cells in the tissue synchronize their gene expression rhythms with neighbors through Delta-Notch signaling, providing local integrity of gene expression patterns. Understanding this synchronization, and it’s role in forming body segments is what brought the four of us together in the first place. 

Previous studies had shown that the treatment of an inhibitor of Delta-Notch signaling, called DAPT, led to formation of defective segments in zebrafish embryos. Some of these studies had also observed the recovery of normal segments after the washout of DAPT (Riedel-Kruse et al. 2007; Liao et al. 2016). These results had been interpreted in terms of desynchronization and resynchronization of oscillators: treatment of DAPT desynchronizes oscillators by inhibiting intercellular coupling through Delta-Notch signaling, and the hallmark spatial wave pattern of gene expression in the PSM is abolished due to the noise in the individual cellular oscillators. However, its washout restores coupling, letting cells gradually resynchronize their oscillators. When the synchrony level reaches a threshold, a normal segment reappears. This desynchronization hypothesis has quantitatively explained several experimental data, but there was a remaining gap in our understanding: how is the tissue-scale pattern reorganized through local coupling?

To address this, we analyzed segment recovery processes with different DAPT washout timing in zebrafish embryos. We unexpectedly found that washing out DAPT at earlier developmental stages caused intermingled segment boundary defects: a defective segment boundary was formed even after some normal segment boundaries were already formed (Fig. 1). This result suggests that the synchrony level fluctuates around the threshold, for some reason. We were very surprised by this result because we expected a monotonic recovery of normal segments based on previous theoretical works on coupled oscillators. Usually, once a population of oscillators gets synchronized, they remain synchronized and a large fluctuation of synchrony level hardly ever occurs. Thus, pattern recovery in the segmenting tissue seemed not so simple.

At this time, there were no transgenic markers of the zebrafish segmentation clock, nor were the microscopes, image processing, and data analysis developed to follow all these oscillating cells during the entire re-synch process (in fact, we are still working on this…).

Therefore, we decided to use a physical model for the segmenting tissue to analyze this phenomenon. We have previously proposed models for the entire presomitic mesoderm and tailbud tissues in lower spatial dimension (1D or 2D; Morelli et al. 2009) or in 3D space but only a part of the tissue (Uriu et al. 2017). This time, we chose to describe the entire tissue in 3D and tried to integrate some of the previous modeling efforts by us and others in this framework (Fig. 2).

In numerical simulations of the model, we found a rotating phase pattern of oscillators, termed a phase vortex, in some situations of resynchronization (Fig. 3A, B). A phase vortex emerges in the tissue by local interactions of oscillators, moves through the tissue along the anterior-posterior axis by cell advection, and generates a defective boundary when it arrives at the anterior part of the PSM. A phase vortex can be formed posterior to the well-synchronized domain in simulation, so it can cause intermingled defective segments, as observed in the experiments.

It turns out that although the formation of a phase vortex is driven by the local interactions, its kinematics is determined by the larger-scale tissue properties. A phase vortex moves from posterior to anterior by cell advection caused by embryonic axis extension. We reasoned that the global tissue properties, such as cell advection and tissue length could affect the pattern recovery in the PSM. Moreover, these tissue properties change with developmental stages. Hence, our physical model predicted that the time to complete recovery, that is, when we do not see any further phase vortices, would depend on the developmental stage at which DAPT washed out. In fact, we observed good agreement between simulations and experiment for the time to complete recovery (Fig. 3C). So, are we done? No. The next key task is to test the theory by observing phase vortices in living tissues. This should be possible by the live imaging of reporters of both oscillatory protein and segment boundaries simultaneously, which requires the long-term imaging, tracking and analysis of the cells in the segmentation clock.

In summary, our study indicated that pattern recovery in the zebrafish segmentation clock occurs at two spatial and temporal scales: quick local synchronization and transport of local patterns through slow tissue shape changes. There’s a nice symmetry to the slow, long-range drift of the four authors, which certainly changed the dynamics of our local communication. Although we were already quite good at video conferencing when the pandemic struck, the available time interval when everyone on the team was awake and alert simultaneously in Japan, Taiwan, Switzerland and Argentina was rather short. Thus, a high signaling strength was an important asset. Indeed, working together on the project over such a long time and through so many life changes was a rewarding experience, and we hope you will enjoy the pattern that self-organized from the process as much as we do.

Uriu K., Liao BK., Oates A.C., Morelli L.G. (2021) From local resynchronization to global pattern recovery in the zebrafish segmentation clock. Elife 10:e61358. doi: 10.7554/eLife.61358. 

References

Liao BK., Jörg D.J., Oates A.C. (2016) Faster embryonic segmentation through elevated Delta-Notch signalling. Nat Commun. 7:11861. doi: 10.1038/ncomms11861.

Riedel-Kruse I.H., Müller C., Oates A.C. (2007) Synchrony dynamics during initiation, failure, and rescue of the segmentation clock. Science 317(5846):1911-5. doi: 10.1126/science.1142538.

Morelli L.G., Ares S., Herrgen L., Schröter C., Jülicher F., Oates A.C. (2009) Delayed coupling theory of vertebrate segmentation. HFSP J. 3(1):55-66. doi: 10.2976/1.3027088.

Uriu K., Bhavna R., Oates A.C., Morelli L.G. (2017) A framework for quantification and physical modeling of cell mixing applied to oscillator synchronization in vertebrate somitogenesis. Biol Open. 6(8):1235-1244. doi: 10.1242/bio.025148.

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This interview, the 93rd in our series, was published in Development earlier this year. 

The plant epidermis is a single layer of cells that forms a crucial barrier to the outside world, but the mechanisms that control epidermal differentiation – in particular the relative importance of position and lineage – remain incompletely understood. A new paper in Development tackles this question in Arabidopsis. To find out more about the story, we caught up with first author Kenji Nagata and his supervisor Mitsutomo Abe, Associate Professor at the University of Tokyo.

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

MA: As a PhD student I researched molecular genetics in Arabidopsis in the lab of Yoshibumi Komeda at Hokkaido University in Sapporo, Japan. I was excited to go to the lab every day, and so fascinated by the beautiful expression patterns of ATML1 and PDF2, twin genes that enabled me to get my PhD in 2001. After my PhD, I joined the lab of Takashi Araki at Kyoto University as an Assistant Professor and started the ‘florigen quest’ with great colleagues. I was fortunate to make a fundamental discovery regarding florigen in 2005, and I am very pleased that FT is now well known as an important component of florigen signalling. After this, I had a great experience working in the lab of Richard Amasino at the University of Wisconsin for two years, and very much enjoyed American life. I then moved to the University of Tokyo and started my own research group in 2009, and keep working on plant molecular genetics.

Our research group has a broad interest in plant development. Some members are involved in elucidating florigen function in Arabidopsis, others (like Kenji) are working on epidermal cell differentiation, and others are interested in the interaction between meristem identity and plant architecture. All have one thing in common: we are focusing on phenomena and molecules that are unique to plants.

Kenji – how did you come to work in Mitsutomo’s lab and what drives your research today?

KN: When I was an undergraduate student, I was very interested in two aspects of sessile plants: the phenotypic plasticity they show in morphology and physiology, and their developmental robustness in terms of patterning. So I looked for a lab that would allow me to explore these issues. I was fortunate to attend one of Mitsutomo’s lectures, where he described his lab’s work on flowering, which is mediated by signals from the external environment, and robust protodermal cell differentiation, which is not influenced by the external environment. I felt that working with him would provide me exciting research opportunities, and decided to join his lab. Curiosity about how the traits unique to sessile plants work and why they developed in an evolutionary context drives my research today.

How has your research been affected by the COVID-19 pandemic?

KN: Due to entry restrictions to the university, we were forced to suspend our experiments and stay at home. Fortunately, none of the members of our lab have caught the virus and all have stayed healthy so far. Although now there are still some restrictions, it is slowly getting back to (a new) normal.

MA: Like most universities and research institutes, only the minimum number of staff necessary to maintain plants and equipment was permitted to enter the lab from spring to summer. Since mid-July, research activities are allowed with the utmost care to prevent the spread of infection. But the number of infected patients in Tokyo is increasing recently, so I’m worried that the lab will be closed again.

Before your work, what was known about the relative roles of lineage and position in plant epidermis differentiation?

KN: It is widely accepted that cell position rather than cell lineage is important for plant cell fate decisions. For example, the inner cells, which derive from occasional periclinal divisions of epidermal cells, develop according to their position rather than their epidermal cell lineage. On the other hand, it is also known that, in shoots, the inner cells never adapt their epidermal identity even if they occupy the outermost position, suggesting that cell lineage is involved in the epidermal cell differentiation. However, it was recently shown that when cells in the inner cell lineage are displaced to the outermost position through laser ablation, they appear to acquire root epidermal cell fate. Thus, it is controversial whether cell lineage indeed affects epidermal cell fate decisions.

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

KN: In this paper, we found that ATML1, a master regulator of protoderm/epidermis differentiation, is only stabilized in the outermost cells derived from the outermost cell lineage. Furthermore, the stability of ATML1 in these cells is conferred by the interaction with its lipid ligand VLCFA-Cers. VLCFA-Cers appears to be polarly localized to peripheral domains in epidermal cells, and passed on to the outermost epidermal cells in a cell position- and lineage-dependent manner. Based on these results, we have proposed a novel model in which ATML1-VLCFA-Cers interaction is restricted to the outermost epidermal cells and consequently restricts protoderm/epidermis differentiation to the appropriate position.

MA: I think for me the key experiment in our paper is the transient induction of ATML1 by a heat shock treatment – I was very excited when Kenji first came to show me the GFP images.

When outermost cells divide asymmetrically, the inner cells inherit ATML1 protein: what then stops them from differentiating as protoderm?

KN: This is because the ATML1 protein in inner cells is rapidly broken down, as shown in the careful observation in the 16-cell-stage embryo of gATML1-EGFP plants, or in our transient ectopic expression assay using HSP::NLS-mCherry; HSP::ATML1-EGFP plants in which the inner cells are not able to differentiate into protoderm. The rapid breakdown of ATML1 protein is due to the absence of VLCFA-Cers, in inner cells. Thus, we propose that VLCFA-Cers act as a landmark of the outermost cell position and lineage, and act as a post-translational signal that mediates positional information.

MA: Epidermis-specific expression of ATML1 and PDF2 is strictly regulated. Therefore, in addition to the mechanism we reported here, I believe that several other regulatory mechanisms are involved in epidermal cell differentiation. I’m really looking forward to the seeing this research progress in the future.

I was very excited when Kenji first came to show me the GFP images

Do lipid-transcription factor complexes mediate positional signals elsewhere in plant development?

KN: We would assume so. Kathrin Schrick and colleagues have shown that START domains from plant HD-Zip transcription factors bind lipid ligands to regulate transcription factor activity in a yeast system. Together with our findings, this suggests that lipids may mediate positional signals and modulate HD-Zip transcription factor activity elsewhere in plant development.

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

KN: I think the most memorable moment was when I observed the outermost cell-specific ATML1-EGFP signal after heat-pulse treatment. This was an important moment when I was certain that our hypothesis was right.

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

KN: The purification of the START domain as a soluble form was challenging. I first tried to purify the full-length ATML1 protein as a soluble form, but I couldn’t obtain it, and ultimately it took over a year to obtain the soluble START domain.

What next for you after this paper?

KN: I am interested in how the ATML1 protein is broken down when VLCFA-Cers is absent – this will deepen our insights about lipid-mediated modulation of transcription factor activity in plants. On the other hand, from an evolutionary perspective, it is important to know whether lipid-transcription factor-based developmental mechanisms also work in the basal land plants or algae.

Where will this story take the Abe lab?

MA: As I mentioned in my biography, since my PhD I’ve been very interested in the molecular mechanism of epidermal cell differentiation. For the past 10 years or so, my lab has been focusing on florigen function and regulation, which involves FT, FD and FE. But I am very pleased that Kenji was interested in and restarted this project 5 years ago. In the future, Kenji and I hope to make exciting discoveries on epidermal cell differentiation.

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

KN: I love to spend my spare time at the Onsen (a Japanese hot spring). After Onsen, I always drink a beer!

MA: In Spring 2019, our lab moved from Hongo to Komaba, which is a 20-min walk from Shibuya city. Shibuya city is a centre for modern culture and entertainment in Japan. I hope I will get to properly enjoy Shibuya life after the COVID-19 pandemic has settled down.

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Development and Disease Models & Mechanisms welcome you to apply for our joint virtual meeting ‘Developmental Disorders: From Mechanism to Treatment‘, which aims to bring together developmental biologists, human geneticists and clinical researchers who are united in the goal of understanding and treating developmental disorders. The underlying causes of developmental disorders – genetic or environmental – are often not understood. Moreover, there is a disconnect between researchers working on animal models of developmental disorders, geneticists trying to identify the genomic lesion responsible, and clinicians hoping to treat affected patients. Given the resulting urgent need to improve communication between these groups, to promote basic research into congenital anomalies and to invest in translating this research to the clinic, this Meeting will focus specifically on building bridges from bench to clinic.

Find out more about the meeting from the organisers Phil Beales, James Briscoe, Monica J. Justice and Lee Niswander in the video below.

Speakers

Jeanne Amiel Institut Imagine, France
Han Brunner Maastricht University Medical Center, The Netherlands
Brian Ciruna The Hospital for Sick Children, Toronto, Canada
Dagan Jenkins University College London, UK
Nicholas Katsanis Rescindo Therapeutics Inc., USA
Karen Liu King’s College London, UK
Stefan Mundlos The Max Planck Institute for Molecular Genetics, Germany
Emily Noël University of Sheffield, UK
Eric Olson UT Southwestern Medical Center, USA
Álvaro Rada-Iglesias IBBTEC, Spain
David Rowitch University of Cambridge, UK
Ian Smyth Monash Biomedicine Discovery Institute, Australia
Lilianna Solnica-Krezel Washington University School of Medicine in St. Louis, USA
Xin Sun University of California San Diego, USA
Lori Sussel University of Colorado, USA

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

This year, the Beddington Medal was awarded to Kristina Stapornwongkul, who did her PhD with Jean Paul Vincent at the Francis Crick Institute. Kristina presented her work at the BSDB/Genetics Society 2021 meeting and we caught up with her after the meeting to find out more about her life in science. Be sure to also check out the profile of Kristina – including a letter from JP Vincent and a list of Kristina’s selected publications – over on the BSDB site.

Where were you born and where did you grow up?

I was born in Giessen and grew up in Weil am Rhein. It’s a small town in Southwest Germany, directly at the border of France and Switzerland. It’s one of the sunniest places in Germany and I love to have a stroll through the vineyards whenever I go back there.

When did you first get interested in science?

I was always fascinated by technology and science, but I only developed a real passion for it in the last two years of high school. The realisation that each of our cells contains the information necessary to build an entire human, really blew my mind and made me want to learn more about how cells work.

How did you come to do a PhD in the lab of JP Vincent?

I think it all started with a zebrafish embryo and a stereo microscope. A few years later, at the end of my Masters studies, I knew that I wanted to do a PhD in the field of developmental biology. The UK has an outstanding developmental biology community and so I applied for the Wellcome Trust PhD programme in Developmental and Stem Cell Biology at UCL. As part of the programme, the students get the opportunity to rotate in three different labs. During my rotation, I realised that the Vincent lab was the perfect fit for me, both scientifically and personally.

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

The concept of morphogen gradient-mediated patterning has always fascinated me with its elegant simplicity: a single signalling molecule that can induce multiple cell fates depending on its concentration. How morphogen gradients form and what determines their shape are therefore important questions in order to understand how robust patterning is achieved in tissues. Several mechanisms by which morphogens might spread have been suggested over the years, with passive diffusion being the most parsimonious one. If such extracellular protein gradients form by simple diffusion, it shouldn’t be that difficult to engineer a morphogen gradient, no? At least that was the idea. So instead of further dissecting how natural morphogen gradients are generated, I wanted to test if an inert protein, such as GFP, could be transformed into a gradient-forming morphogen. Apart from probing whether diffusion is sufficiently reliable as a morphogen-transport mechanism, I was hoping that this synthetic approach would also help to uncover general principles and constraints that shape extracellular gradients. To do this work in vivo, I used the Drosophila wing pouch, one of the best studied model systems for morphogen gradient formation.

In your 2020 Science paper you describe your efforts to engineer a morphogen gradient, replacing Dpp with GFP. What did this technique reveal about how morphogens work?

The thing with engineering a synthetic morphogen gradient is that, even if it works, there is no guarantee that natural morphogens work exactly the same way. Nevertheless, our approach enabled us to show that protein gradients can, in principle, form by passive diffusion and that such gradients are reliable enough to pattern a tissue in vivo. It also made it feasible to specifically manipulate properties, such as binding affinities or expression levels, and test their effect on GFP gradient shape. Combining this with a modelling approach, we were therefore able to gain a good understanding of what each component was doing in our synthetic system.

Of course, we encountered several difficulties while building the GFP morphogen system and these were probably the most informative, because natural morphogen gradients that form by diffusion will encounter them as well. For instance, it became clear that secreted GFP can be lost from the tissue and end up in the larval blood, the hemolymph. This was really a big issue for the patterning performance of the GFP gradient. In fact, all secreted morphogens interact to a with components in the extracellar matrix and this is probably one important mechanism to regulate morphogenetic retention in epithelia.

If I had to summarise our findings in a sentence, I would probably say that a combination of high-affinity signalling receptors and low-affinity non-signalling receptors is sufficient to allow diffusing GFP to mimic the organising activity of a natural morphogen.

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

As you can imagine this project involved many ‘trial and error’ experiments, and of course a good amount of luck. When you try to engineer something, it might not work for so many reasons. Even if your general design is good, expression levels might be too high or too low, or your synthetic receptor pair is not recycled efficiently (yes, that was an issue). So I think one of the most abiding memories of my PhD was when I saw for the first time that GFP in combination with GFP-responsive Dpp receptors was able to rescue growth and patterning of the fly wing pretty well. I expected a bit of a rescue, but I never thought that a two-component system could substitute that successfully an endogenous extracellular morphogen system, which not only consists of ligands and receptors but also of many extracellular regulators. My first thought was, ‘I must have messed up the genetics. The rescue is too good’. So, after checking everything three times, I went to JP and showed him the wing. His first response was, ‘Are you sure, you didn’t mess up the genetics?’.

You recently published a review making ‘the case for diffusion’. Why did you need to make this case?

Morphogen-mediated patterning has been studied extensively in a variety of model systems. However, the question of how morphogens spread in a tissue has remained quite controversial, especially in epithelial tissues. For instance, it has been suggested that diffusion is difficult to regulate and not reliable enough to generate robust extracellular gradients. As an alternative, active transport mechanisms, such as planar transcytosis or specialised filopodia (cytonemes), have been proposed. In our review, we try to give a comprehensive overview of the existing evidence from different model systems and conclude that there is strong evidence that morphogens disperse by diffusion-based mechanisms. In particular, we highlight how the tissue architecture and the ligand’s biochemical properties impose constraints on diffusion-based gradient formation and how components of the extracellular matrix help to overcome them.

So after your PhD you’ve recently moved to Barcelona: what are you doing there and how are you finding the city compared to London?
I started as a postdoctoral fellow in Vikas Trivedi’s and Miki Ebisuya’s lab at EMBL Barcelona. We use aggregates of mouse embryonic stem cells as minimal model systems to study symmetry breaking and germ layer specification. London is amazing and definitely has a special place in my heart, but I have to admit that I am really in love with Barcelona. Being able to go for a swim after work and having tons of herbs that happily grow in the sun, is really amazing!

Longer term, do you know if you plan to stay in science?

Working in science is a huge privilege and I really appreciate the chance to interact with so many bright and inspiring people. Currently, I can’t imagine a more enjoyable job. However, being able to stay in science depends on many different factors and so I always try to stay open-minded.

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

I expect that we will have a much better understanding of the molecular mechanisms of human development. Already now, stem cell-based in vitro systems give us first insights into human organogenesis – a developmental stage in which functional studies were basically impossible before. As a consequence, we will probably also see a much stronger engagement of developmental biologists with the field of disease modelling.

Similarly, our research will depend less and less on the classical model systems. With CRISPR and stem cells, we will probably be able to widen our perspective on development by investigating anything from small insects to large mammals. I think it will be very exciting to see the differences and similarities we can find!

But I’m sure that’s not the only exciting direction developmental biology will take! I think developmental biology will be even more interdisciplinary (if that’s even possible) in ten years. Personally, I’m quite interested in the role of metabolism in development, but I’m sure there are also many more interesting intersections that we will further explore.

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

I like to go climbing, swimming, hiking… pretty much all kinds of outdoor activities. Travelling is also a big passion of mine and I hope it will soon be possible again. 

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Some readers of the Node might already be familiar with preLights, another community site run by The Company of Biologists which aims to highlight new preprints from across the biological sciences. Most of the preLights community members are early-career researchers (PhD students and postdocs), but recently, preLights has found a new role as a teaching aid. Both the NYU Peer Review and Utrecht Protein Folding and Assembly courses have started using group preprint review projects as a tool to learn about critical reading and peer review. To learn more about how preLights has helped them teach these courses, preLights spoke to Gira Bhabha at NYU, and Tessa Sinnige at Utrecht University.

Read more on the preLights website here.

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This interview, the 92nd in our series, was published in Development last year. 

In many animal embryos, the tail bends ventrally as it grows, but the underlying mechanisms driving this multi-tissue deformation have been difficult to study. A new paper in Development uses the simple chordate Ciona as a model to study this widely conserved process. To find out more about the story, we met the paper’s two first authors, Qiongxuan Lu and Yuan Gao, and their supervisor Bo Dong, Professor at the Ocean University of China in Qingdao, China.

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

BD: I got my PhD from the Institute of Oceanology, Chinese Academy of Sciences (IOCAS), and then worked as a postdoc in the Sars International Centre for Marine Molecular Biology in the University of Bergen in Norway. After that, I went to RIKEN Centre for Developmental Biology (CDB) in Kobe, Japan, and worked on Drosophila tracheal tube geometry control. In 2014, I came back to the Ocean University of China (OUC) in Qingdao and established my own laboratory working on organ morphogenesis and evolution. My laboratory is principally interested in uncovering the cellular, mechanical and biochemical signalling networks that interact to drive the diverse morphogenetic processes during organ formation and tissue regression using marine ascidians and flies as models.

Qiongxuan and Yuan – how did you come to work in Bo’s lab and what drives your research today?

QL: I first met Bo in 2014 when he gave a lecture related to Ciona notochord tubulogenesis in 2014. From this lecture I was attracted to the field of morphogenesis, and the long-lasting question of how functional shape is generated. I then joined Bo’s lab two years later to investigate the mechanical role of the notochord in chordate embryogenesis. It was really memorable when I took a time-lapse movie on a Ciona embryo without a chorion from zygote to tailbud stage. Indeed, from this movie, we noticed and were curious about the phenomenon of the tail always bending ventrally after the initial tailbud stage, which led us to the story you see in the paper.

YG: Biomechanics has been recognized as the most promising direction of theoretical and applied mechanics. In the Institute of Biomechanics and Medical Engineering (IBME) in Tsinghua University, we focus not only on scientific mechanics problems in crucial biological problems at different length scales, but also emphasize the clinical issues of major diseases. As a PhD student majoring in biomechanics, I am particularly interested in how mechanical forces tune morphogenesis during development, and my PhD project is to develop physical/mechanical models to elucidate these underlying mechanisms.

The mechanisms behind embryonic tail bending in Ciona are so attractive. Thanks to the meeting of Prof. Bo Dong and my supervisor Prof. Xi-Qiao Feng, I was lucky enough to join in this project. Qiongxuan had performed a lot of experiments and obtained interesting and effective results. Based on this, I developed a physical model to further understand the mechanical role of each tissue during the tail bending process in Ciona embryos.

What is the current position of developmental biology and evo-devo research in China?

BD: Currently there is a pretty large developmental biology community in China. We have our own society and hold annual meetings. There are several hundred research groups working on developmental biology-related studies using either classical model animals such as zebrafish, Drosophila and Caenorhabditis elegans, or non-standard model organisms such as ascidian, amphioxus, ciliates and lamprey. Most aspects of developmental biology research – such as organogenesis, pattern formation, physiological metabolism, and regeneration – are categorised as basic research, so the main source of funding is the Natural Science Foundation of China. The evo-devo field is relatively smaller, but the increase in genomic data, new gene editing methods and the fast development of imaging techniques provides us with the opportunity to do evo-devo research in evolutionarily important animals.

Before your work, what was our understanding of how embryonic tail bending was controlled?

QL, YG, BD: Embryonic tail bending is an evolutionarily-conserved morphogenetic process in early embryogenesis for most invertebrates and vertebrates. This large-scale morphogenetic event has been long known about, but the underlying mechanisms have not been investigated. A possible reason is tissue-bending and tissue-folding at the embryo scale is difficult to study because of the anatomical complexity of many model animals. Before our publication, it was thought that embryonic tail bending is a passive process achieved by the physical barrier of the chorion that confines the tail, bending it during elongation.

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

QL, YG, BD: In this paper, we first show that in the urochordate Ciona, embryonic tail bending is not dependent on the chorion, but rather is a self-organized and genetically programmed active process. We then found that actomyosin is asymmetrically accumulated at the ventral side of the notochord, and cell proliferation of the dorsal tail epidermis is faster than the ventral counterpart during bending. Through a combination of genetic perturbation and chemical drug manipulation, we reveal that both asymmetrical notochord contractility and differential epidermis proliferation are required for the tail-bending process. We further developed a model with experimentally measured parameters to simulate the bending process. The simulation result shows that the asymmetrical notochord contractility is sufficient to drive the tail bending, whereas the differential cell proliferation is a passive response to mechanical forces. Thus, we reveal a mechanism of asymmetrical notochord contractility coordinated with differential epidermis proliferation that drives embryonic bending. The main implications of this work are not only revealing that embryonic bending within the chorion is driven by intrinsic forces, but also demonstrating how the different tissues of the tail interact and coordinate to sculpt the embryonic shape.

Do you have any idea about what causes the ventral enrichment of actomyosin in the notochord?

QL, YG, BD: This is a really interesting question that is worthy of further investigation. We actually have screened some candidate signalling molecules using in situ hybridization, but have so far failed to get positive results. We knew from the published literature that some proteins, such as those in the extracellular matrix, also show polarity during notochord morphogenesis. Interestingly, during notochord convergent extension, the notochord preferentially accumulates laminin, a basement membrane marker, dorsally, and atypical protein kinase C, an apical cell polarity molecule, ventrally, which might provide a polarizing cue for polarized actomyosin enrichment.

Bending appears to be conserved with many other vertebrate and tunicate embryos: do you think it serves a particular purpose for the embryo? And is the mechanism you’ve discovered in Ciona likely to also be conserved?

QL, YG, BD: Von Baer’s laws say that vertebrate embryos converge on a common physical structure and hence show a similar morphology during early embryogenesis, called the phylotypic stages. For example, at the beginning of neurulation, chordate embryos are commonly C-shaped. We think that bending of the embryonic tail could help embryos elongate continuously within the chorion without mechanical damage. It definitely saves space to contain the elongated embryos within the chorion.

In this paper, we found that the polarized contractility of the notochord plays a major role in shaping the bending tail at early tailbud stages, whereas biased epidermal proliferation ensures the robustness of tail bending at later tailbud stages. However, our data did not rule out the possibility that other tissues and their interactions also contribute to embryonic tail bending. Indeed other data suggest that the role of the notochord in driving embryonic tail bending depends on the synergistic effect of other tissues. In more structurally-complex vertebrate systems, we really do not know whether notochord contractility still plays the active role: further investigations are definitely needed.

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

QL: I think the best moment for me was finding that actomyosin was temporarily enriched at the ventral side of the notochord. This interesting observation prompted us to investigate what role this polarised actomyosin might have in tail bending.

YG: A rational and effective model is only part of the way to success. The moments that most stick with me are when I find out a proper theory to depict the biological process. In this research, for example, we incorporated the active contraction of tissues into the model by using volumetric growth theory. Then it became easy to analyse the mechanical role of each tissue during tail bending.

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

QL: Sure, I definitely had a lot of them. For example, when we tried to confirm the role of the notochord in driving tail bending, our initial idea was to isolate the notochords from tailbud embryos and test whether they could bend spontaneously by the ventrally enriched actomyosin. This embryonic manipulation was rather challenging due to the tiny notochord located in the middle of the tail, surrounded by several tissues. We were stuck for a long time until we realized that we could try to think in an alternative way, and this transition led to the idea that physical modelling could also help us to address this question. Although I experienced so many failed attempts, I certainly learnt a lot from them, such as to always keep an open mind, and that interdisciplinary knowledge is essential for troubleshooting.

YG: As I am not a biology major, the technical terms sometimes become the obstacle to my understanding of the biological process. Likewise, my collaborators are not very good at mechanics and, at the first stage, it was a challenge to make the physical model understood. Fortunately, constant communication and discussions with my collaborators helped me overcome these difficulties.

Interdisciplinary knowledge is essential for troubleshooting.

What next for you after this paper?

QL: I am currently a postdoctoral fellow in the Umeå Centre for Molecular Medicine in Sweden, studying the neuronal basis of O₂ sensing in C. elegans. I’m getting exposed to different fields, and I hope these interdisciplinary combinations will help me to explore more interesting questions.

YG: I will finish my dissertation in about six months. Meanwhile, I am looking for a postdoc position at present: the mechanical mechanisms underlying morphogenesis are intriguing and I hope to continue with this subject.

Where will this story take the Dong lab?

BD: Based on this and our previous work, we are recognizing the important roles of mechanical signalling in pattern formation during embryogenesis. For example, in this story, we believe that the faster cell proliferation in the dorsal midline epidermis can release the accumulated mechanical stress generated by asymmetrical notochord contractility. The follow up question is whether mechanochemical feedback exists between mechanical stretching and differential epidermis proliferation. If yes, how is the mechanical signalling sensed by the dorsal epidermis, and how does it respond?

Another question we are interested in pursuing is polarity signalling, which has important implications for tissue mechanics. Compared with the anatomically complex vertebrates, the Ciona embryonic tail is structurally simple, providing an excellent model to understand how polarity signalling impacts multi-tissue development.

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

QL: I spend most of my spare time either playing tennis, walking around our campus or climbing mountains nearby in Qingdao. These activities provide me a different kind of excitement outside of the lab, and more importantly, they enable me to balance my personal life and work.

YG: We are a big family in IBME. In our spare time, we often do sports together, like basketball and swimming. Besides, Beijing is an ancient and fascinating city, and I like to explore it with friends if we are free at weekends.

BD: I like to stay with my family during my spare time. We often climb Laoshan mountain and have weekend dinners together eating Qingdao’s delicious seafood. Sometimes, I also enjoy drinking Qingdao beer with my friends, which really can be relaxing, especially on summer nights.

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Written by Shuangshuang Du, Rebecca Starble, and Lauren Gonzalez from the Yale Genetics Department.

We face a historical moment in which more and more women are pursuing scientific careers, but we have failed to support their success in leadership positions. This is in part because leadership styles that are authentic to their identities are not well represented by those who are currently in power. Opportunities for professional development could begin to offer young scientists techniques to overcome this gender barrier.

Despite this urgent need, training in interpersonal relationship skills is often absent in the graduate school curriculum. “Looking around the lab, I see talented graduate researchers undertaking challenging research projects who struggle not just with the science, but also because of the need to navigate the sparsity of female role models, confront cultural differences, and maintain self-belief,” said Shuangshuang Du, a Genetics student from Dr. Valentina Greco’s lab at Yale.

Du spearheaded the organization of a leadership workshop for graduate students in 2020, inspired by the first-ever female in science workshop for postdocs at Yale organized by Dr. Sara Gallini in 2019. She reached out to the Yale Biological and Biomedical Sciences (BBS) program to design a process by which this training could be accessed by the entire graduate student body, partnering with workshop liaison Dr. Jennifer Claydon to poll interests for such a workshop among BBS students and identify possible sources of funding. In December 2020, 16 Yale BBS women graduate researchers from five departments across the university participated in the inaugural iteration of this course.

This course was taught by hfp consulting, a firm that specializes in leadership in science. Over the four half-day sessions, the facilitators and participants covered various skills critical to becoming empowered leaders in STEM, including effective communication, active listening, assertiveness, addressing imposter fears, and developing a peer support group. They approached these topics in a highly interactive way: participants were encouraged to engage with the content, the trainers, and each other through a combination of large-group and small-group activities to practice using these skills.

For example, in a module on conflict resolution, participants worked through their own real-life scenarios in small groups to get feedback from each other on how to deal with conflict using clear and respectful communication. This gave participants a safe, supportive environment to practice using these leadership skills, thus building participants’ confidence to apply these skills in their professional lives after the workshop ended.

This approach was transformative. “This course was incredibly valuable for my development as a female leader in science by enabling me to identify and take advantage of my strengths, learn what style of leadership is best for me, and expand my repertoire of interpersonal skills that are beneficial both professionally and personally” said Molly Bucklin, a PhD candidate in the department of Immunobiology. Renee Wasko, a PhD candidate in the department of Molecular, Cellular, and Developmental Biology, noted that although she is “someone who regularly attends other self-help/career development seminars, this was the first experience that felt eye-opening and realistically implementable.”

Participants also developed a strong community which didn’t end when the official course was over. “This program created a lasting support network for me,” said Wasko. “I still regularly connect with the other members of my cohort to discuss the topics and tools we learned and how they pertain to our lives currently.” This community has been especially valuable during the COVID-19 pandemic, when many students have felt disconnected from their support networks, and the pressures of graduate school have remained high.

Investing in young women early in their scientific careers is essential to preserve this diverse talent within academia because it provides them not only leadership skills, but also a space and a language to discuss their professional challenges and ambitions. This course serves as a blueprint to embed that learning within the Yale PhD curriculum, equipping young leaders with the tools to overcome systemic barriers and shift the culture of STEM towards one of inclusivity and empowerment.

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