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

The preprints this month are hosted on bioRxiv and arXiv – use these links below 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

Developmental biology

| Patterning & signalling

Metabolic control by the Bithorax Complex-Wnt signaling crosstalk in Drosophila

Rajitha-Udakara-Sampath Hemba-Waduge, Mengmeng Liu, Xiao Li, Jasmine L. Sun, Elisabeth A. Budslick, Sarah E. Bondos, Jun-Yuan Ji

Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities

Victorio Palacio, Anna Pancho, Angela Morabito, Jonas Malkmus, Zhisong He, Geoffrey Soussi, Rolf Zeller, Barbara Treutlein, Aimée Zuniga

Growth-induced physiological hypoxia correlates with growth deceleration during normal development

Yifan Zhao, Cyrille Alexandre, Gavin Kelly, Gantas Perez-Mockus, Jean-Paul Vincent

Metabolic activities are selective modulators for individual segmentation clock processes

Mitsuhiro Matsuda, Jorge Lázaro, Miki Ebisuya

mTORC2-mediated cell-cell interaction promote BMP4-induced WNT activation and mesoderm differentiation

Li Tong, Faiza Batool, Yueh-Ho Chiu, Yudong Zhou, Xiaolun Ma, Santosh Atanur, Wei Cui

Hypoxia-Sonic Hedgehog Axis as a Driver of Primitive Hematopoiesis Development and Evolution in Cavefish

Corine M. van der Weele, Katrina C. Hospes, Katherine E. Rowe, William R. Jeffery

Illuminating morphogen and patterning dynamics with optogenetic control of morphogen production

Dirk Benzinger, James Briscoe

Combinatorial Wnt signaling landscape during brachiopod anteroposterior patterning

Bruno C. Vellutini, José M. Martín-Durán, Aina Børve, Andreas Hejnol

Depolarization induces calcium-dependent BMP4 release from mouse embryonic palate mesenchyme

Mikaela L Follmer, Trevor Isner, Yunus H. Ozekin, Claire Levitt, Emily Anne Bates

Lineage-specific CDK activity dynamics characterize early mammalian development

Bechara Saykali, Andy D. Tran, James A. Cornwell, Matthew A. Caldwell, Paniz Rezvan Sangsari, Nicole Y. Morgan, Michael J. Kruhlak, Steven D. Cappell, Sergio Ruiz

Dachsous and Fat coordinately repress the Dachs-Dlish-Approximated complex to control growth

Hitoshi Matakatsu, Richard G. Fehon

Notch1 is required to maintain supporting cell identity and vestibular function during maturation of the mammalian balance organs

Alison Heffer, Choongheon Lee, Joseph C. Holt, Amy E. Kiernan

Bisphenol AF induces overactivation of primordial follicles via Hippo signaling and causes premature ovarian insufficiency in micev

Xiaoyang Liu, Mingxi Yu, Tiancheng Wang, Xiangdong Hu, Rui Zhong, Yuan Xiao, Yan Xu, Mei Zhang, Shuang Tang

Decorin enhances metabolic maturation by activating AMPK-PGC1A pathway in cardiac organoids

Myeong-Hwa Song, Seongmin Jun, Seung-Cheol Choi, Ji Eun Na, Im Joo Rhyu, Sun Wook Hwang, Minji Jeon, Do-Sun Lim

The Drosophila hematopoietic niche assembles through collective cell migration controlled by neighbor tissues and Slit-Robo signaling

Kara A. Nelson, Kari F. Lenhart, Lauren Anllo, Stephen DiNardo

| Morphogenesis & mechanics

Contractile fibroblasts are recruited to the growing mammary epithelium to support branching morphogenesis

Jakub Sumbal, Robin P. Journot, Marisa M. Faraldo, Zuzana Sumbalova Koledova, Silvia Fre

Effects and phenotypic consequences of transient thyrotoxicosis and hypothyroidism at different stages of zebrafish Danio rerio (Teleostei; Cyprinidae) skeleton development

Vasily Borisov, Fedor Shkil

Congenital heart defects differ following left versus right avian cardiac neural crest ablation

Tatiana Solovieva, Marianne E. Bronner

Age-associated increased stiffness of the ovarian microenvironment impairs follicle development and oocyte quality and rapidly alters follicle gene expression

Sara Pietroforte, Makenzie Plough, Farners Amargant

Distinct functions of three Wnt proteins control mirror-symmetric organogenesis in the C. elegans gonad

Shuhei So, Masayo Asakawa, Hitoshi Sawa

Control of epiblast cell fate by mechanical cues

Charlène Guillot, Yannis Djeffal, Mattia Serra, Olivier Pourquié

Mechanical Strain Activates Planar Cell Polarity Signaling to Coordinate Vascular Cell Dynamics

Lieke Golbach, Tanumoy Saha, Maria Odenthal-Schnittler, Jenny Lücking, Ana Velic, Emir Bora Akmeric, Dorothee Bornhorst, Oliver Popp, Philipp Mertins, Felix Gunawan, Holger Gerhardt, Boris Macek, Britta Trappmann, Hans J. Schnittler, Milos Galic, Maja Matis

Increase in ER-mitochondria contacts and mitochondrial fusion are hallmarks of mitochondrial activation during embryogenesis

Anastasia Chugunova, Hannah Keresztes, Roksolana Kobylinska, Maria Novatchkova, Thomas Lendl, Marcus Strobl, Michael Schutzbier, Gerhard Dürnberger, Richard Imre, Elisabeth Roitinger, Pawel Pasierbek, Alberto Moreno Cencerrado, Marlene Brandstetter, Thomas Köcher, Benedikt Agerer, Jakob-Wendelin Genger, Andreas Bergthaler, Andrea Pauli

| Genes & genomes

Transcriptomic Analysis of the Spatiotemporal Axis of Oogenesis and Fertilization in C. elegans

Yangqi Su, Jonathan Shea, Darla DeStephanis, Zhengchang Su

Heterochromatin protein ERH represses alternative cell fates during early mammalian differentiation

Andrew Katznelson, Blake Hernandez, Holly Fahning, Jingchao Zhang, Adam Burton, Maria-Elena Torres-Padilla, Nicolas Plachta, Kenneth S. Zaret, Ryan L. McCarthy

Microphthalmia and disrupted retinal development due to a LacZ knock-in/knock-out allele at the Vsx2 locus

Francesca R. Napoli, Xiaodong Li, Alan A. Hurtado, Edward M. Levine

Neural crest and periderm-specific requirements of Irf6 during neural tube and craniofacial development

Shannon H. Carroll, Sogand Schafer, Eileen Dalessandro, Thach-Vu Ho, Yang Chai, Eric C. Liao

The requirement of GW182 in miRNA-mediated gene silencing in Drosophila larval development

Eriko Matsuura-Suzuki, Kori Kiyokawa, Shintaro Iwasaki, Yukihide Tomari

The non-canonical thioreductase TMX2 is essential for neuronal survival during embryonic brain development

Jordy Dekker, Wendy Lam, Herma C. van der Linde, Floris Ophorst, Charlotte de Konink, Rachel Schot, Gert-Jan Kremers, Leslie E. Sanderson, Woutje M. Berdowski, Geeske M. van Woerden, Grazia M.S. Mancini, Tjakko J. van Ham

The Conserved Transcription Factor Krüppel Regulates the Survival and Neurogenesis of Mushroom Body Neuroblasts in Drosophila Adult Brains

Jin Man, Xian Shu, Haoer Shi, Xue Xia, Yusanjiang Abula, Yuu Kimata

Spinal motor neuron development and metabolism are transcriptionally regulated by Nuclear Factor IA

Julia Gauberg, Kevin B. Moreno, Karthik Jayaraman, Sara Abumeri, Sarah Jenkins, Alisa M. Salazar, Hiruy S Meharena, Stacey M Glasgow

RFC1 regulates the expansion of neural progenitors in the developing zebrafish cerebellum

Fanny Nobilleau, Sébastien Audet, Sanaa Turk, Charlotte Zaouter, Meijiang Liao, Nicolas Pilon, Martine Tétreault, Shunmoogum A. Patten, Éric Samarut

| Stem cells, regeneration & disease modelling

Ephrin Forward Signaling Controls Interspecies Cell Competition in Pluripotent Stem Cells

Junichi Tanaka, Yuri Kondo, Masahiro Sakurai, Anri Sawada, Youngmin Hwang, Akihiro Miura, Yuko Shimamura, Dai Shimizu, Yingying Hu, Hemanta Sarmah, Zurab Ninish, James Cai, Jun Wu, Munemasa Mori

Single-nucleus transcriptomic analysis reveals the regulatory circuitry of myofiber XBP1 during regenerative myogenesis

Aniket S. Joshi, Micah B. Castillo, Meiricris Tomaz da Silva, Preethi H. Gunaratne, Radbod Darabi, Yu Liu, Ashok Kumar

Niche cytoskeletal architecture is required for proper stem cell signaling and oriented division in the Drosophila testis

Gabriela S. Vida, Elizabeth Botto, Stephen DiNardo

Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome

Mary-Bronwen L. Chalkley, Lindsey N. Guerin, Tenhir Iyer, Samantha Mallahan, Sydney Nelson, Mustafa Sahin, Emily Hodges, Kevin C. Ess, Rebecca A. Ihrie

Single-cell transcriptome unravels spermatogonial stem cells and dynamic heterogeneity of spermatogenesis in seasonal breeding teleost

Yang Yang, Yinan Zhou, Gary Wessel, Weihua Hu, Dongdong Xu

Mimicking physiological stiffness or oxygen levels in vitro reorganizes mesenchymal stem cells machinery toward a more naïve phenotype

Inês Caramelo, Vera M. Mendes, Catarina Domingues, Sandra I. Anjo, Margarida Geraldo, Carla M. P. Cardoso, Mário Grãos, Bruno Manadas

The Hippo/YAP Pathway Mediates the De-differentiation of Corneal Epithelial Cells into Functional Limbal Epithelial Stem Cells In Vivo

Yijian Li, Lingling Ge, Bangqi Ren, Xue Zhang, Zhiyuan Yin, Hongling Liu, Yuli Yang, Yong Liu, Haiwei Xu

Harnessing the regenerative potential of interleukin11 to enhance heart repair

Kwangdeok Shin, Anjelica Rodriguez-Parks, Chanul Kim, Isabella M. Silaban, Yu Xia, Jisheng Sun, Chenyang Dong, Sunduz Keles, Jinhu Wang, Jingli Cao, Junsu Kang

Inhibition of CELA1 Improves Septation in the Mouse Hyperoxia Model of Impaired Alveolar Development

Noah J. Smith, Rashika Joshi, Hitesh Desmukh, Jerilyn Gray, Andrea D. Edwards, Elham Shahreki, Brian M. Varisco

Lineage tracing of Shh+ floor plate cells and dynamics of dorsal-ventral gene expression in the regenerating axolotl spinal cord

Laura Isabella Arbanas, Emanuel Cura Costa, Osvaldo Chara, Leo Otsuki, Elly Margaret Tanaka

Regeneration-specific promoter switching facilitates Mest expression in the mouse digit tip to modulate neutrophil response

Vivian Jou, Sophia M. Peña, Jessica A. Lehoczky

Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model

Ahmed K. Elsayed, Noura Aldous, Nehad Alajez, Essam M. Abdelalim

Stochastic cell-intrinsic stem cell decisions control colony growth in planarians

Tamar Frankovits, Prakash Varkey Cherian, Yarden Yesharim, Simon Dobler, Omri Wurtzel

An iPSC-based model of Jacob Syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with X aneuploid cells

V. Astro, K. Cardona-Londoño, L.V. Cortés-Medina, R. Alghamdi, G. Ramírez-Calderón, F. Kefalas, J. Dilmé-Capó, S. Radío, A. Adamo

Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets

Melis Akgün Canan, Corinna Cozzitorto, Michael Sterr, Lama Saber, Eunike S.A. Setyono, Xianming Wang, Juliane Merl-Pham, Tobias Greisle, Ingo Burtscher, Heiko Lickert

Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios

Fabian Doktor, Rebeca Lopes Figueira, Victoria Fortuna, George Biouss, Kaya Stasiewicz, Mikal Obed, Kasra Khalaj, Lina Antounians, Augusto Zani

Stable platelet production via the bypass pathway explains the long-term reconstitution capacity of hematopoietic stem cells

Shoya Iwanami, Toshiko Sato, Hiroshi Haeno, Longchen Xu, Keimyo Imamura, Jun Ooehara, Xun Lan, Hiromitsu Nakauchi, Shingo Iwami, Ryo Yamamoto

Divergent roles of SOX2 in human and mouse germ cell specification related to X-linked gene dosage effects

Wenteng He, Qing Luo, Jian Zhao, Mengting Wang, Luohua Feng, Allan Zhao, Ahmed Reda, Eva Lindgren, Jan-Bernd Strukenborg, Jiayu Chen, Qiaolin Deng

Hepatocyte-derived extracellular vesicles regulate liver regeneration after partial hepatectomy

Mina McGinn, Christopher Rabender, Ross Mikkelsen, Vasily Yakovlev

Delivery of A Jagged1-PEG-MAL hydrogel with Pediatric Human Bone Cells Regenerates Critically-Sized Craniofacial Bone Defects

Archana Kamalakar, Brendan Tobin, Sundus Kaimari, M. Hope Robinson, Afra I. Toma, Timothy Cha, Samir Chihab, Irica Moriarity, Surabhi Gautam, Pallavi Bhattaram, Shelly Abramowicz, Hicham Drissi, Andrés J. García, Levi B. Wood, Steven L. Goudy

A human-specific, concerted repression of microcephaly genes contributes to radiation-induced growth defects in forebrain organoids

Jessica Honorato Ribeiro, Emre Etlioglu, Jasmine Buset, Ann Janssen, Hanne Puype, Lisa Berden, André Claude Mbouombouo Mfossa, Winnok H. De Vos, Vanessa Vermeirssen, Sarah Baatout, Nicholas Rajan, Roel Quintens

Genetic variation modulates susceptibility to aberrant DNA hypomethylation and imprint deregulation in naïve pluripotent stem cells

C Parikh, RA Glenn, Y Shi, K Chatterjee, EE Swanzey, S Singer, SC Do, Y Zhan, Y Furuta, M Tahiliani, E Apostolou, A Polyzos, R Koche, JG Mezey, T Vierbuchen, M Stadtfeld

| Plant development

Systemic mRNA transport depends on m5C methylation, nuclear mRNA export factors and developmental phase changes

Ying Xu, András Székely, Steffen Ostendorp, Saurabh Gupta, Melissa Tomkins, Lei Yang, Federico Apelt, Yan Zhao, Eleni Mavrothalassiti, Linda Wansing, Julia Kehr, Eleftheria Saplaoura, Friedrich Kragler

OsAAI1-OsMADS25 module orchestrates root morphogenesis by fine-tuning IAA in drought stressed rice

Ning Xu, Rui Luo, Qing Long, Jianmin Man, Jiaxi Yin, Haimin Liao, Meng Jiang

The Arabidopsis splicing factor PORCUPINE/SmE1 orchestrates temperature-dependent root development via auxin homeostasis maintenance

Nabila El Arbi, Sarah Muniz Nardeli, Jan Šimura, Karin Ljung, Markus Schmid

Unveiling Stem Cell Induction Mechanisms From Spatiotemporal Cell-Type-Specific Gene Regulatory Networks In Postembryonic Root Organogensis

Javier Cabrera, Alvaro Sanchez-Corrionero, Angels de Luis Balaguer, Laura Serrano-Ron, Cristina del Barrio, Pilar Cubas, Pablo Perez-Garcia, Rosangela Sozzani, Miguel Moreno-Risueno

Histidine limitation causes alteration in the TOR network and plant development

Amandine Guérin, Caroline Levasseur, Aline Herger, Dominik Renggli, Alexandros Georgios Sotiropoulos, Gabor Kadler, Xiaoyu Hou, Myriam Schaufelberger, Christian Meyer, Thomas Wicker, Laurent Bigler, Christoph Ringli

Cell fate plasticity of xylem-pole-pericycle in Arabidopsis roots

Xin Wang, Lingling Ye, Jing Zhang, Charles W. Melnyk, Ari Pekka Mähönen

Manipulation of Photosensory and Circadian Signalling Restricts Developmental Plasticity in Arabidopsis

Martin William Battle, Scott Fraser Ewing, Cathryn Dickson, Joseph Obaje, Kristen N. Edgeworth, Rebecca Bindbeutel, Rea Antoniou Kourounioti, Dmitri A. Nusinow, Matthew Alan Jones

Dissecting the genetic regulation of lateral root development in tomato under salt stress

Maryam Rahmati Ishka, Hayley Sussman, Jiantao Zhao, Eric Craft, Li’ang Yu, Andrew Nelson, Miguel Pineros, Mark Tester, Dorota Kawa, Zhangjun Fei, Magdalena M. Julkowska

Actin isovariant ACT2-mediated cellular auxin homeostasis regulates lateral root organogenesis in Arabidopsis thaliana

Aya Hanzawa, Arifa Ahamed Rahman, Abidur Rahman

An AINTEGUMENTA phospho-switch controls bilateral stem cell activity during secondary growth

Wei Xiao, Ling Yang, David Molina, Houming Chen, Shan Yu, Yingjing Miao, Dagmar Ripper, Shulin Deng, Martin Bayer, Bert De Rybel, Laura Ragni

ESR2 orchestrates cytokinin dynamics leading to developmental reprogramming and green callus formation

Yolanda Durán-Medina, David Díaz-Ramírez, Humberto Herrera-Ubaldo, Maurizio Di Marzo, Andrea Gómez Felipe, J. Erik Cruz-Valderrama, Carlos A. Vázquez, Herenia Guerrero-Largo, Lucia Colombo, Ondrej Novak, Stefan de Folter, Nayelli Marsch-Martínez

The O-Fucosyltransferase SPINDLY Attenuates Auxin-Induced Fruit Growth by Inhibiting ARF6 and ARF8 binding to Coactivator Mediator Complex in Arabidopsis

Yan Wang, Seamus Kelley, Rodolfo Zentella, Jianhong Hu, Hua Wei, Lei Wang, Jeffrey Shabanowitz, Donald F. Hunt, Tai-ping Sun

Plant height defined growth curves during vegetative development have the potential to predict end of season maize yield and assist with mid-season management decisions

Dorothy D. Sweet, Julian Cooper, Cory D. Hirsch, Candice N. Hirsch

Epigenetic memory of temperature sensed during somatic embryo maturation in 2-year-old maritime pine trees

J.-F. Trontin, M.D. Sow, A. Delaunay, I. Modesto, C. Teyssier, I. Reymond, F. Canlet, N. Boizot, C. Le Metté, A. Gibert, C. Chaparro, C. Daviaud, J. Tost, C. Miguel, M.-A. Lelu-Walter, S. Maury

In a nutshell: pistachio genome and kernel development

Jaclyn A. Adaskaveg, Chaehee Lee, Yiduo Wei, Fangyi Wang, Filipa S. Grilo, Saskia D. Mesquida-Pesci, Matthew Davis, Selina C. Wang, Giulia Marino, Louise Ferguson, Patrick J Brown, Georgia Drakakaki, Adela Mena-Morales, Annalisa Marchese, Antonio Giovino, Esaú Martínez, Francesco Paolo Marra, Lourdes Marchante Cuevas, Luigi Cattivelli, Paolo Bagnaresi, Pablo Carbonell-Bejerano, Grey Monroe, Barbara Blanco-Ulate

| Evo-devo

Brachiopod genome unveils the evolution of the BMP–Chordin network in bilaterian body patterning

Thomas D. Lewin, Keisuke Shimizu, Isabel Jiah-Yih Liao, Mu-En Chen, Kazuyoshi Endo, Noriyuki Satoh, Peter W. H. Holland, Yue Him Wong, Yi-Jyun Luo

The joint evolution of separate sexes and sexual dimorphism

Thomas Lesaffre, John R. Pannell, Charles Mullon

Horn size is linked to Sertoli cell efficiency and sperm size homogeneity during sexual development in common eland (Taurotragus oryx)

Eliana Pintus, Radim Kotrba, José Luis Ros-Santaella

Lepidopteran scale cells derive from sensory organ precursors through a canonical lineage

Ling S. Loh, Kyle A. DeMarr, Martina Tsimba, Christa Heryanto, Alejandro Berrio, Nipam H. Patel, Arnaud Martin, W. Owen McMillan, Gregory A. Wray, Joseph J. Hanly

Temporal dynamics of gene expression during metamorphosis in two distant Drosophila species

Aleksandra M Ozerova, Dina A. Kulikova, Michael B Evgen’ev, Mikhail S. Gelfand

Multiplexed transcriptomic analyses of the plant embryonic hourglass

Hao Wu, Ruqiang Zhang, Karl J. Niklas, Michael J. Scanlon

Separating the genetic and environmental drivers of body temperature during the development of endothermy in an altricial bird

Lucy A. Winder, Jacob Hogger Gadsby, Eleanor Wellman, Joel L. Pick, Mirre J.P. Simons, Terry Burke

Convergent evolution of sex chromosomes in palms

H. Tessarotto, T. Beulé, E. Cherif, J. Orjuela, A. Lindstrom, A. Lemansour, M. Dahme, S. Santoni, J. Käfer, F. Aberlenc

Same trait, different genes: pelvic spine loss in three brook stickleback populations in Alberta

Jonathan A. Mee

Evolutionary bursts drive morphological novelty in the world’s largest skinks

Ian G. Brennan, David G. Chapple, J. Scott Keogh, Stephen Donnellan

Ecdysteroid-dependent molting in tardigrades

Shumpei Yamakawa, Andreas Hejnol

Cell Biology

N-Cadherin mediated cell rearrangements shape embryonic macrophage cluster

Jacob Hasenauer, Xiang Meng, Honor Scarborough, Jasmine A. Stanley-Ahmed, Darius Vasco Köster, Aparna Ratheesh

UNC-6/Netrin promotes both adhesion and directed growth within a single axon

Ev L. Nichols, Joo Lee, Kang Shen

Transcription templated assembly of the nucleolus in the C. elegans embryo

Nishant Kodan, Rabeya Hussaini, Stephanie C. Weber, Jane Kondev, Lishibanya Mohapatra

Systematic analysis of protein stability associated with species-specific developmental tempo

Mitsuhiro Matsuda, Henrik M. Hammarén, Jorge Lázaro, Mikhail M. Savitski, Miki Ebisuya

The zebrafish as a new model for studying chaperone-mediated autophagy unveils its role in spermatogenesis

Maxime Goguet, Emilio J Vélez, Simon Schnebert, Karine Dias, Vincent Véron, Alexandra Depincé, Florian Beaumatin, Amaury Herpin, Iban Seiliez

Contribution of the neuron-specific ATP1A3 to embryonic spinal circuit emergencev

Sarah Dinvaut, Sophie Calvet, Jean-Christophe Comte, Raphael Gury, Olivier Pascual, Maelys André, Rosaria Ferrigno, Jérôme Honnorat, Frédéric Moret, Guillaume Marcy, Julien Falk, Valérie Castellani

Multi-omics analyses and machine learning prediction of oviductal responses in the presence of gametes and embryos

Ryan M Finnerty, Daniel J Carulli, Akshata Hedge, Yanli Wang, Frimpong Boadu, Sarayut Winuthayanon, Jianlin Cheng, Wipawee Winuthayanon

Maternal total sleep deprivation causes oxidative stress and mitochondrial dysfunction in oocytes associated with fertility decline in mice

Ziyun Yi, Qiu-xia Liang, Qian Zhou, Yang Lin, Qing-ren Meng, Jian Li, Yihua Lin, Chunhui Zhang, Heide Schatten, Jie Qiao, Qing-Yuan Sun

The cell cycle oscillator and spindle length set the speed of chromosome separation in Drosophila embryos

Yitong Xu, Anna Chao, Melissa Rinaldin, Alison Kickuth, Jan Brugués, Stefano Di Talia

PCM1 conveys centrosome asymmetry to polarized endosome dynamics in regulating daughter cell fate

Xiang Zhao, Yiqi Wang, Vincent Mouilleau, Ahmet Can Solak, Jason Garcia, Xingye Chen, Christopher J. Wilkinson, Loic Royer, Zhiqiang Dong, Su Guo

Identification of BiP as a temperature sensor mediating temperature-induced germline sex reversal

Jing Shi, Danli Sheng, Jie Guo, Fangyuan Zhou, Shaofeng Wu, Hongyun Tang

Fibrotic Extracellular Matrix Preferentially Induces a Partial Epithelial-Mesenchymal Transition Phenotype in a 3-D Agent Based Model of Fibrosis

Kristin P. Kim, Christopher A. Lemmon

Cell type-specific regulation by different cytokinetic pathways in the early embryo

Caroline Q. Connors, Sophia L. Martin, Julien Dumont, Mimi Shirasu-Hiza, Julie C. Canman

Imp and Syp in vivo temporal RNA interactomes uncover networks of temporal regulators of Drosophila brain development

Jeffrey Y Lee, Niles Huang, Tamsin J Samuels, Ilan Davis

Comprehensive characterization of mitochondrial bioenergetics at different larval stages reveals novel insights about the developmental metabolism of Caenorhabditis elegans

Danielle F. Mello, Luiza Perez, Christina M. Bergemann, Katherine S. Morton, Ian T. Ryde, Joel N. Meyer

Modelling

The Molecular Basis of Differentiation Wave Activity in Embryogenesis

Bradly Alicea, Surosh Bastani, Natalie K. Gordon, Susan Crawford-Young, Richard Gordon

Statistical description of mobile oscillators in embryonic pattern formation

Koichiro Uriu, Luis G Morelli

Statistical description of mobile oscillators in embryonic pattern formation

Koichiro Uriu, Luis G. Morelli

How cells stay together; a mechanism for maintenance of a robust cluster explored by local and nonlocal continuum models

Andreas Buttenschön, Shona Sinclair, Leah Edelstein-Keshet

Minimal cellular automaton model with heterogeneous cell sizes predicts epithelial colony growth

Steffen Lange, Jannik Schmied, Paul Willam, Anja Voss-Böhme

Tools & Resources

Efficient generation of human dendritic cells from iPSC by introducing a feeder-free expansion step for hematopoietic progenitors

Zahra Elahi, Vanta Jameson, Magdaline Sakkas, Suzanne K Butcher, Justine D Mintern, Kristen J Radford, Christine A Wells

Interaction between gene expression and morphokinetic parameters in undisturbed human embryo culture

Hui Xiao, Adam Stevens, Helen L. Smith, Karolina Szczesna, Maria Keramari, Gregory Horne, Andras Dinnyes, Susan J. Kimber, Pietro Lio, Daniel R. Brison

Enhanced Plasmid-Based Transcriptional Activation in Developing Mouse Photoreceptors

Brendon M. Patierno, Mark M. Emerson

A Pluripotent Stem Cell Platform for in Vitro Systems Genetics Studies of Mouse Development

Rachel A. Glenn, Stephanie C. Do, Karthik Guruvayurappan, Emily K. Corrigan, Laura Santini, Daniel Medina-Cano, Sarah Singer, Hyein Cho, Jing Liu, Karl Broman, Anne Czechanski, Laura Reinholdt, Richard Koche, Yasuhide Furuta, Meik Kunz, Thomas Vierbuchen

Functional imaging of whole mouse embryonic development in utero

Jiejun Zhu, Dongming He, Mengzhu Sun, Hanming Zheng, Zihao Chen, Jin Yang, Chengqi Lin, Yun Stone Shi, Lei Sun, Zhihai Qiu

Mass Generation and Long-term Expansion of Hepatobiliary Organoids from Adult Primary Human Hepatocytes

Ary Marsee, Arabela Ritchie, Adam Myszczyszyn, Shicheng Ye, Jung-Chin Chang, Arif Ibrahim Ardisasmita, Indi P Joore, Jose Castro-Alpízar, Sabine A Fuchs, Kerstin Schneeberger, Bart Spee

Unveiling Vertebrate Development Dynamics in Frog Xenopus laevis using Micro-CT Imaging

Laznovsky Jakub, Kavkova Michaela, Reis Alice, Robovska-Havelkova Pavla, Krivanek Jan, Zikmund Tomas, Kaiser Jozef, Buchtova Marcela, Harnos Jakub

Transcriptomic comparison of in vitro models of the human placenta

Samantha Lapehn, Sidharth Nair, Evan J Firsick, James MacDonald, Ciara Thoreson, James A Litch, Nicole R Bush, Leena Kadam, Sylvie Girard, Leslie Myatt, Bhagwat Prasad, Sheela Sathyanarayana, Alison G Paquette

Chemically induced cell plasticity enables the generation of high-fidelity embryo model

Huanhuan Li, Jiahui Huang, Wei Guan, Jinyi Wu, Haiping Luo, Litao Chang, Haiyong Zhao, Chuanxin Chen, Yake Gao, Jian Zhang, José C. R. Silva

Neural tube organoid generation: a robust and reproducible protocol from single mouse embryonic stem cells

Teresa Krammer, Elly M. Tanaka

An efficient method for immortalizing mouse embryonic fibroblasts

Srisathya Srinivasan, Hsin-Yi Henry Ho

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The LAG-R framework (Laboratory Animal Genetic Reporting) has just been published in Nature Communications with Lydia Teboul, head of our Molecular Cell Biology team at the Mary Lyon Centre at MRC Harwell and Guillaume Pavlovic, Head of Unit, Genetic Engineering and Model Validation Department at the Institut Clinique de la Souris– PHENOMIN– IGBMC, as corresponding authors. The LAG-R framework is a set of guidelines to support more complete documentation of the genetic make-up of animals that are used in research, with the aim of bolstering reproducibility, reliability, and overall scientific rigour.

The biomedical research community is addressing many different factors that lead to problems with reproducibility, including via the implementation of the PREPARE guidelines, which aim to improve experimental design, and the ARRIVE guidelines, which aim to improve reporting of animal research experiments. However, a need remains for a more comprehensive description of the genetics of research animals, as differences in genetic background that are too often perceived as subtle can have a significant impact on phenotype and genetic modifications are rarely fully documented.

The LAG-R guidelines are designed to improve the documentation that is associated with animal research and to be applicable to the full range of animal species used. Standardising and improving genetic documentation will enhance research reliability and reduce wastage of resources and animals by cutting down on the reconstitution of missing information or on follow-up experiments that unknowingly use animals with different genetics.

The LAG-R guidelines have been developed by an international team that includes authors from 15 countries, working within a number of international consortia, including the Asian Mouse Mutagenesis Resource Association, the International Mammalian Genome Society, the International Mouse Phenotyping Consortium, the European Research Infrastructure for Modelling Human Diseases (INFRAFRONTIER), the International Society for Transgenic Technologies, the Mutant Mouse Resource & Research Centres, and Phenomics Australia.

The authors said: “The LAG-R Guidelines are not about influencing what models researchers use for their research. They are about standardising the way the genetics of these animals are documented. This framework is intended to be simple to adopt and takes into account the diversity of research environments where animals are used. Documentation is a key part of research reproducibility!“

The authors are working to create a publicly available resource web page to facilitate the uptake of the guidelines by the community. Watch this space!

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What is this?

The video depicts the formation of the so-called lateral line in a transgenic zebrafish that I took when I was a student in Tatjana Piotrowski’s lab at the Stowers Institute for Medical Research (Kansas City, MO, USA). Cells of the lateral line use collective cell migration —sort of a cellular ‘Conga’ formation— to move from the head of the animal into the trunk and deposit volcano-shaped structures called neuromasts.

Where can the lateral line be found?

Fishes (bony, such as the zebrafish; and cartilaginous, such as sharks and rays) and amphibians (such as frogs and salamanders).

How was this video taken?

This is a video of a transgenic zebrafish expressing a fluorescent protein in the lateral line Tg(clndb:lynGFP). The video was taken live using a Zeiss 780 confocal microscope.

What does the lateral line do?

The lateral line is a mechanosensory organ that aquatic animals use to orient themselves in the water using neuromasts that cover the entire body of the animal (like in the picture below). These neuromasts are the sensory unit of the lateral line due to the presence of specialized sensory cells called hair cells (that do indeed have little ‘hairs’, but we call them kinocilia and stereocilia) that respond to the water flow. This movement is translated into synaptic information and is sent to the brain, where it is used to convey positional information. The lateral line also allows fishes to display the so-called ‘schooling behavior’, a kind of collective animal behavior that is commonly seen in documentaries showing fishes moving together

Why should people care about this?

Due to the transparency, rapid development and gene conservation of zebrafish, the lateral line is an outstanding model to study two processes: collective cell migration, and hair cell regeneration.

The migrating primordia depicted in the video deploy the same molecular and cellular tools healthy and cancer cells use to migrate. Thus, studying migration of the lateral line primordia can help us understanding collective cell migration in health and disease.

One interesting property about hair cells is that they are also present in humans, but they are in the inner ear and they are used for hearing. When we age, or under some non-physiological conditions, we lose hair cells forever. Fishes, on the other hand, can regenerate their hair cells upon loss; therefore, studying how fish regenerate their hair cells may give us clues that can be used to restore hearing in humans that have lost hair cells.

How would you explain this to an 8-year-old?

During their development, fishes have little groups of cells that move all together all over the body. These cells then form garlic-bulb shaped structures that fishes use to swim, due to the presence of prickly cells called hair cells. People also have hair cells — but not all over their bodies, but inside your ears — that we use for hearing.

Where can people find more about it?

https://en.wikipedia.org/wiki/Lateral_line

“PCP and Wnt pathway components act in parallel during zebrafish mechanosensory hair cell orientation” Navajas Acedo et al. 2019

https://www.nature.com/articles/s41467-019-12005-y (in this open access publication you can find the first video of the post, plus some others related to the lateral line and its formation)

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In this post, I invite you to join me on the journey through our recent article titled “Two Orthogonal Differentiation Gradients Locally Coordinate Fruit Morphogenesis.” This story started when I joined the lab of Daniel Kierzkowski at the Institut de Recherche en Biologie Végétale (IRBV) at the Université de Montréal as a visiting PhD student in January 2020. My main goal was to learn how to perform live imaging in plants and analyze the output data. Daniel invited me to contribute to his project related to fruit morphogenesis, and I believe it fit perfectly my interest in fruit development. The central question of this project was straightforward: what are the growth patterns underlying gynoecium development from its initiation to the final shape? I started working on that project just one week prior to the COVID outbreak in Canada. I had my first confocal experiment running the day before the University of Montreal recommended all foreign internship students to go back home due to upcoming pandemics. I decided to stay and found myself “stuck” in Montreal. This situation led to my most productive period when I spent several hours, days and weeks in the microscopy room. It was just me and the confocal microscope in the entire building (a quiet solitary experience). Walking through the deserted corridors evoked a mix of sadness and loneliness, but there was also a rewarding feeling of the “perfect samples” I just imaged with the confocal microscope. We were all astonished to see that my samples could grow for two consecutive weeks, from small primordium to fully developed gynoecium (future fruit)!

Simultaneously, I juggled the demands of writing my PhD thesis, preparing one of my papers derived from my PhD, and gearing up for my thesis defense, which, due to the outbreak, had to be conducted online. It was a challenging time, but one that ultimately shaped me and my research journey in unexpected ways.

After successfully obtaining high-quality images of the gynoecium, we started the image analysis using MorphoGraphX. This part would not have been possible without the help of my colleague Elvis Branchini, whose dedication helped us segment and quantify growth in thousands of cells (from around 50 to 11000 per sample). This initial analysis represents, to our knowledge, the first comprehensive growth analysis spanning organ initiation to full expansion in plants. I take great pride in this significant achievement.

We started to dissect in detail different analyses on our gynoecium data including cell expansion, size, anisotropy, proliferation, and differentiation from each single cell. By deconstructing growth directions, both medial-lateral and longitudinal, we observed a medial-lateral growth gradient early in development. This observation contrasts with other plant organs, such as leaves, sepals, and stamen, which typically exhibit a basipetal (top-to-bottom) gradient of growth. This result was surprising for us: an organ that comes from an ancestral leaf has a different behavior. Then we started to look for explanations and formulated different hypotheses. Among these, the role of auxin — a favorite hormone in the plant scientific community — was promising within the context of our study.

Perspective from this Study:

From this study, we found that two distinct, time-shifted, and competing differentiation gradients govern gynoecium morphogenesis: an early mediolateral growth gradient and a late longitudinal growth gradient. A compelling next step would be to explore how these gradients interact. It would be fascinating to examine whether the early differentiation of the valve restricts the typical basipetal gradients from spreading through the organ, similar to what is observed in leaves, sepals, and petals. Additionally, investigating how the timing of these gradient establishments affects the final fruit shape in Brassicaceae, which exhibits a wide variety of fruit shapes, could provide valuable insights.

My contribution:

The methods and approaches I developed for this paper are now being used in Daniel’s lab. These techniques will facilitate a more detailed investigation into fruit development across different species, improving our understanding of how fruits develop in the Brassicaceae family. This study offers a thorough and detailed atlas of growth patterns during gynoecium development. While many fascinating questions about fruit shape remain, this research paves the way for a deeper exploration of fruit development, particularly focusing on the shape and mechanical interactions within its different tissues.

My eureka moment:

Each step of the project felt like a eureka moment to me, but one has stayed with me: when we observed a full series growing continuously for two consecutive weeks. It was a delightful surprise. Additionally, each session of live imaging proved to be both gratifying and occasionally frustrating, yet undeniably worthwhile. My colleague and friend Binghan can attest to this, having shared the excitement, and participated in insightful discussions about our findings.

Bumps along the way:

Like many academic research projects, our journey with the gynoecium project was marked by challenges. We faced setbacks, moments of being stuck, and occasional frustration. I lost count of the numerous samples that did not survive or perished along the way. I recall one particular incident during my chemical treatment experiment. The plants were ready, I meticulously dissected numerous samples to maximize our chances of success. It was my fourth day of imaging, and the samples were growing really happily. Then, a disaster struck on a Sunday evening. I went to switch on the confocal microscope, and guess what? I could not initiate the system, it crashed, I wanted to cry at that moment (but I did not). Then, I lost my samples. I had to repeat the experiment again.

Similar situations occurred a couple more times, leading my colleagues to jokingly label me as having bad luck. However, I learned to cultivate resilience and approach failed experiments with a sense of humor —’Here we go, again!’— became my mantra in the realm of science.

Along the way, I learned invaluable lessons, the journey of trial and error ultimately led to new discoveries, making the effort worthwhile. When I look back and see everything we have made, I think it was all worth the effort! Despite the technical obstacles, I persevered, allowing me to expand my skills in problem-solving, critical thinking, and patience.

Our experience with the review process for our article submission was surprisingly smooth, especially compared to the tales I have heard from my colleagues. I have no complaints in that regard; both the editors and the reviewers were prompt in their responses. The comments of all the reviewers helped us improve our story. Finally, our story has found a home where it can be read.

My next step:

I have found myself profoundly inspired by this project. This experience has solidified my conviction that within science, limitless opportunities await those who approach their work with love, passion, and genuine curiosity. As scientists, we are not just observers; we are creators, empowered to innovate and explore the unknown. Following this project, I am eager to continue working on plant development and plant hormones. My focus will be on synthetic biology, and I aim to learn and utilize cutting-edge techniques such as single-cell sequencing, proteomics and CRISPR-Cas. I want to combine my knowledge of plant development and synthetic biology with one of my passions: microscopy. I’m excited to see what discoveries await on my next journey!

In the end:

The journey through this paper has significantly enhanced and refined several skills crucial for my scientific career. This accomplishment is deeply indebted to the invaluable assistance of my colleagues, who dedicated countless hours to segmenting hundreds of cells. Furthermore, the support of my friends and peers has been invaluable. Finally, I want to express my gratitude to my former boss, Daniel, for his ongoing support, insightful feedback, and discussions throughout my stay in his lab.

I invite you to read our story: Two orthogonal differentiation gradients locally coordinate fruit morphogenesis https://www.nature.com/articles/s41467-024-47325-1

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Basement membranes (BMs) are thin, specialized extracellular matrices that surround most tissues and organs (Jayadev and Sherwood, 2017). These meshworks serve as scaffolds for cell adhesion, influencing cell signaling, cell migration, proliferation, and differentiation (Sherwood, 2021; Yurchenco, 2011). Moreover, dysregulation of BM remodeling lead to disturbed tissue and organ development or disease (Sekiguchi, R and Yamada, K. M., 2018). Recent publications indicate that establishment of BM heterogeneity might be important for tissue and organ sculpting (Agarwal et al., 2022; Harmansa et al., 2023; Harunaga et al., 2014; Kyprianou et al., 2020; Serna-Morales et al., 2023; Uwe Töpfer et al., 2022). However, how this heterogeneity is induced and how this leads to organ sculpting is largely unknown.

In our recent publication (Töpfer et al., 2024), we identified two AdamTS matrix proteases required for the proper elongated shape of the egg chamber. Knockdown of stall or AdamTS-A results in rounder eggs from early elongation phase on. While the phenotypes look very similar, the molecular mechanisms by which they act are different.
Using CRISPR/Cas, we tagged both proteins with sfGFP and found a dynamic expression, resulting in higher protein enrichment in the terminal regions (at the most anterior and posterior regions). We were able to detect Stall in early stalk cell precursors and stalk cells as well as a strong expression later in the polar cells with a gradual expression at the terminal regions of stage 8 egg chambers. AdamTS-A was uniformly expressed in all somatic precursors of follicle cells, but becomes more strongly enriched at the terminal regions in stage 8 egg chambers, too.
Next, we used fly lines with GFP-tagged ECM components to study the proteases’ role in ECM remodeling. We found that Stall is required to establish basement membrane heterogeneity by locally limiting Collagen IV protein density. In contrast to a lower fluorescence signal in control egg chambers in the posterior region, stall knockdown led to a nearly uniform protein level of Collagen IV along the anterior -posterior axis.
Using high-resolution microscopy, we studied the pattern of fiber-like structures embedded in the BM. We found that the knockdown of AdamTS-A results in a disturbed BM micropattern. BM fiber-like structures were shorter and smaller in AdamTS-A knockdown egg chambers. Maturation (length and proper orientation) of BM fiber-like structures has been associated with egg chamber rotation. Accordingly, we also found that AdamTS-A is required for proper egg chamber rotation, hence knockdown of AdamTS-A results in a premature stop.
We performed Atomic force microscopy to measure the stiffness of the BM. In both knockdown conditions, BM stiffness was globally increased, what goes along with increased apical pSRC level. Finally, we found slower E-Cad recovery in a FRAP experiment and a disturbed cell aspect ratio in the central regions. This data indicates that basement membrane remodeling by AdamTS-A and Stall influences gradual BM remodeling which induces BM stiffness and cell shape globally, which is required for organ shape.

References

Agarwal, P., Shemesh, T. and Zaidel-Bar, R. (2022). Directed cell invasion and asymmetric adhesion drive tissue elongation and turning in C. elegans gonad morphogenesis. Developmental Cell 57, 2111-2126.e6.
Harmansa, S., Erlich, A., Eloy, C., Zurlo, G. and Lecuit, T. (2023). Growth anisotropy of the extracellular matrix shapes a developing organ. Nat Commun 14, 1220.
Harunaga, J. S., Doyle, A. D. and Yamada, K. M. (2014). Local and global dynamics of the basement membrane during branching morphogenesis require protease activity and actomyosin contractility. Developmental Biology 394, 197–205.
Jayadev, R. and Sherwood, D. R. (2017). Basement membranes. Current Biology 27, R207–R211.
Kyprianou, C., Christodoulou, N., Hamilton, R. S., Nahaboo, W., Boomgaard, D. S., Amadei, G., Migeotte, I. and Zernicka-Goetz, M. (2020). Basement membrane remodelling regulates mouse embryogenesis. Nature 582, 253–258.
Sekiguchi, R and Yamada, K. M. (2018). Basement Membranes in Development and Disease. Current Topics in Developmental Biology 130, 143–191.
Serna-Morales, E., Sánchez-Sánchez, B. J., Marcotti, S., Nichols, A., Bhargava, A., Dragu, A., Hirvonen, L. M., Díaz-de-la-Loza, M.-C., Mink, M., Cox, S., et al. (2023). Extracellular matrix assembly stress initiates Drosophila central nervous system morphogenesis. Developmental Cell 58, 825-835.e6.
Sherwood, D. R. (2021). Basement membrane remodeling guides cell migration and cell morphogenesis during development. Current Opinion in Cell Biology 72, 19–27.
Töpfer, U., Guerra Santillán, K. Y., Fischer‐Friedrich, E. and Dahmann, C. (2022). Distinct contributions of ECM proteins to basement membrane mechanical properties in Drosophila. Development 149 (10): dev200456.
Töpfer, U., Ryu, J., Guerra Santillán, K. Y., Schulze, J., Fischer-Friedrich, E., Tanentzapf, G. and Dahmann, C. (2024). AdamTS proteases control basement membrane heterogeneity and organ shape in Drosophila. Cell Reports 43, 114399.
Yurchenco, P. D. (2011). Basement Membranes: Cell Scaffoldings and Signaling Platforms. Cold Spring Harbor Perspectives in Biology 3, a004911–a004911.

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Since the sequencing of GFP in the 1990’s, interrogation of biological questions using transgenic model organisms expressing genetically engineered fluorescent molecules has exploded across many biological fields.  Living organisms are superiorly suited to these inquiries as they’re the native environment of the mysteries being explored.  A myriad of biological tools, designed to elucidate these perplexities of nature, have been developed, but most exciting amongst them are the burgeoning systems of optical tools for use in live organismal studies.  To address the necessity for a chronicled repertoire of the tools in this toolkit, in a recent review, KD Fenelon et al. 2024 compiled a reference for scientists seeking to understand or develop new transgenic models expressing optical tools for visualization, quantification, and/or manipulation of subcellular and tissue-level molecular processes in vivo ¹.  These purely transgenic tools can be generally broken up into three categories: tags for visualizing biological phenomena, sensors for measuring biological function, and optogenetics for manipulating biological processes (Fig. 1). 

Tagging systems have advanced dramatically from the days of basic fluorescent protein fusions to label the fused protein.  The slow maturation rates of fluorescent proteins has been remedied through development of secondary attachment fluorescent systems whereby an aqueous pool of fluorescent proteins is maintained which produces sharp puncti through binding to target proteins.  Additionally, ever more creative manipulations and modifications of the Cas9 enzyme allows for easy and efficient labeling of DNA sequences.  Furthermore, transcription and RNA dynamics can be visualized in vivo through the use of several available tagging techniques, including by introducing stem loops to an RNA sequence to be bound by a fluorescently labeled coat protein or by engineering the RNA binding domain of the Pumilio system to label endogenous sequences.

Indeed, fluorescent labels have further evolved to be utilized as sensors to measure molecular-level phenomena².  Forster Resonance Energy Transfer (FRET) and Bioluminescence Resonance Energy Transfer (BRET) allow for measurement of distances between compatible fluorescent and bioluminescent proteins which are used to sense a myriad of physical phenomena including proximity, tension, and metabolite levels.  Furthermore, split and circularly permuted fluorophore allow for proximity and conformational detection.

Perhaps most excitingly, optically sensitive proteins have now been leveraged to facilitate light-mediated, physical control of fusion protein constructs.  These extraordinary tools are broadly labeled ‘optogenetics’ and enable a wide-range of external subcellular manipulations³.  Optogenetic systems, such as PixD, CRY2/CIB1, iLID/SspB, COP-1/UVR8, & Q-PAS1/BphP1, enable light-dependent, reversible binding/dissociation of fusion protein constructs.  Similarly, PhoCl facilitates irreversible, light-dependent cleavage of fusion protein constructs.  Analogous to these, systems such as PixE/PixD and CRY2 facilitate light-dependent oligomerization of proteins.  Optogenetic systems including the light-oxygen-voltage (LOV) domain family sterically rearrange to ‘hide’ or expose protein sequences within a cryptic domain in response to light.  Further, a wide variety of naturally occurring and genetically engineered opsins can now be used to induce membrane transfer of a wide variety of ions and metabolites via light exposure.

Already, there is an explosion of new and exciting innovative and complex applications for these tools (See Fig. 2).  For example, LANSTRAP⁴ facilitates light-dependent nuclear export and attachment to the cell membrane of transcription factors while LINXnano⁵ facilitates light-induced mitochondrial membrane detachment and nuclear import of target transcription factors.  Another inventive example is the BLITz⁶ system which keeps proteins tethered to the cell membrane until light exposure induces an irreversible cleavage via a split protease.  Further, gene expression can be controlled without requiring cytoplasmic accumulation of transcription factors: BICYCL⁷ and iLight⁸ facilitate toggling gene expression on an off by changing the wavelength of light exposure.  These are but a few of the exciting and invaluable tools currently available to the modern genetic engineer, warranting their compilation in the resource published recently by the Koromila Lab^9,10 in PLOS Genetics.

References

1. Fenelon, K.D., Krause, J. & Koromila, T. PLoS Genet 20, e1011208 (2024).
2. Wang, M., Da, Y. & Tian, Y. Chem Soc Rev 52, 1189–1214 (2023).
3. Fischer, A.A.M., et al.. Curr Opin Chem Biol 70, (2022).
4. Yumerefendi, H. et al. ChemBioChem (2018).
5. Yumerefendi, H. et al. Nat Chem Biol 12, (2016).
6. Lee, D. et al. Nat Methods 14, 495–503 (2017).
7. Jang, J. et al. Nat Methods 20, 432–441 (2023).
8. Kaberniuk, A.A.,et al. Nat Commun 12, 1–12 (2021).
9. Fenelon, K.D. et al. Biol Open 11, (2022).
10. Stevens, L.M. et al. PLoS Genet 17, e1009544 (2021).

Biorender and Adobe Illustrator were used in creation of the illustrations.

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In this interview, we caught up with Indulekha M S, who joined the Indian Society of Developmental Biologists (InSDB) as their Community Manager at the end of 2023.

What is your background and what made you decide to join the InSDB as their Community Manager?

I did an integrated bachelor’s and master’s of science from the Indian Institute of Science Education and Research (IISER) in Trivandrum, Kerala. I majored in biology and was working in a drosophila genetics lab at the time. Initially, like most of my peers, I wanted to go ahead with a graduate program. But somewhere in the five years of my time at IISE, I got interested in the communications side of science. I had a few stints with a couple of scicomm groups- I worked as an audio editor, produced video interviews, and so on. After graduation, I wanted to do this full-time, and that was when I came across the advert for the community manager position for InSDB. The job description seemed perfect for me, and I applied right away. That’s how I got in.

What does the role of InSDB’s Community Manager entail?

My role is to initiate new activities at InSDB and execute them. I engage with the members and produce stories, interviews, and other forms of content. I also take up new publications in developmental biology and publish lay summaries. Along with this, I manage the InSDB website and social media handles and keep an active online presence. I also coordinate and help organize the InSDB meetings. There’s also a small administrative side to the role: I help take care of the day-to-day functioning of the society. We want to initiate outreach activities that popularize developmental biology, and recently, as a part of this, I visited a few institutes and interacted with the students and faculty there to increase the visibility of InSDB.

Can you give an introduction about the InSDB to the Node readers?

InSDB is the national society that represents researchers in the area of developmental biology field in India. It was formed in the 1970s, and currently, we have members across all career stages, from undergrads to faculties. The society hosts its flagship meeting every two years, and researchers come together and present their work. We had our 2024 meeting in February this year, and the next meeting will be held in 2026. Along with that, we are now planning for smaller, focused meetings and more outreach initiatives. We also have an active website where you can access a variety of resources. When someone becomes a member of InSDB, you get access to the network of developmental biologists and can also avail reduced registration fees for meetings and workshops we organize.

There’s a recent revamp of InSDB’s website. What are the new features and how can researchers make use of the resources on the website?

The new website is a platform made for members to connect with each other and access resources. The site was designed keeping this in mind. One of the key features of the site is that once you become a member, you can ping other members directly from the website. There’s also the forum– a place where you can discuss relevant topics. The forum is your place if you want to discuss a newly published paper or get tips on something. We also publish events – meetings/workshops/journal clubs – and we advertise opportunities in devbio-related fields. The website also has a lot of teaching and learning resources that one can use. We try to add more resources frequently and all the things we curate are to help researchers/students in different ways.

Our audience can also put up events that they are organizing or that they know of. They can also feature Ph.D, postdoc, or internship openings in their labs. We also invite resource submissions that others can make use of.

Are there ways for researchers to contribute to InSDB?

Yes, of course! In fact, we want more people to contribute to InSDB. We welcome articles and perspectives from our readers. Our community blog has some articles written by graduate students. If anyone out there is interested in contributing, they can send a mail to info@insdb.in. It is our members who make the community, so if there is an idea for a new initiative that you would like to see InSDB implement, we are all ears for it.

Any exciting plans/ upcoming projects you’re doing for InSDB?

Yes! We want to do many things at InSDB, but first, we want to connect better with the members and then take InSDB and developmental biology to the more general audience. We have started this by showcasing our members’ stories on the website. You can find these interviews here. As I mentioned before, we want to initiate outreach activities for the non-specialist audience. We are building this up right now. We had our first outreach event of the year at the BLiSc campus in Bangalore, where we had a whole exhibition displayed for high school students. It was a fun event and there’ll be more such events in the future!

Finally, what do you like to do in your free time?

I am new to the city that I currently live in – Bangalore. My weekends are spent roaming around the city and indulging in the local cuisine. If not for that, I am a homebody and spend most of my time reading or trying to find new hobbies.

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While the vertebrate body consists of diverse structures formed during embryogenesis, there is a limited number of genetic regulatory modules that are repurposed in different developmental contexts. For example, the same gene, or group of genes, often play different roles in development of different embryonic structures. That is the case for the hindlimbs and external genitalia – appendages that share many developmental mechanisms and regulatory genes. In our recently published paper, we show that in the absence of Tgfbr1, precursor of external genitalia changes its response to common regulatory signals from genital-specific to limb-specific and adopts limb fate.

Tgf-beta signaling regulates the trunk to tail transition

When I started my PhD project I wanted to study the development of the main body axis. The vertebrate body consists of three main compartments: head, trunk and tail. During embryogenesis these compartments form sequentially, and together with timely transitions between them outline the body plan of an adult organism. I was particularly interested in the trunk to tail transition.

It has long been known that Growth Differentiation Factor 11 (Gdf11) is a key regulator of the trunk to tail transition [1]. In Gdf11 mutant embryos this transition is delayed, resulting in extended trunk length. However, the exact mechanism underlying Gdf11 activity remains unclear. Gdf11 is a signaling molecule of the transforming growth factor beta (Tgf-beta) superfamily and its activity regulating the trunk to tail transition is mediated by binding to a complex of membrane receptors. The partial redundancy with other Tgf-beta ligands has complicated studying molecular mechanism behind Gdf11 [2]. We though that removing one of the membrane receptors could solve this redundancy problem and help us understand genetic regulation of the transition. Previous studies have shown that Transforming growth factor beta receptor 1 (Tgfbr1) mediates Gdf11 activity in the context of trunk to tail transition, so we targeted this receptor and created a mutant mouse line [3], [4].

From the main body axis to appendages

This model helped us uncover many aspects of Tgf-beta regulation of the trunk to tail transition. Normally, during this transition, the embryo stops producing mesoderm associated with the development of internal organs and the body wall and induces caudal body appendages, such as hindlimbs and external genitalia. We showed that Tgfbr1 knock out embryos fail in all these processes [5]. However, due to Tgfbr1’s involvement in heart development and angiogenesis, which results in midgestational lethality, we could only evaluate the early phenotype in Tgfbr1 mutants [6]. To study the effects of Tgfbr1 deficiency at later developmental stages we designed another mouse model where this gene is inactivated after its requirement for heart development. We induced Tgfbr1 deletion in the embryo by administering tamoxifen to pregnant females.

Obtaining late-stage mutant embryos required crossing mice with compound genotypes and optimizing tamoxifen delivery. After months of adjustments in the protocol, we observed the first embryo with a distinct phenotype. It was very fragile and had multiple malformations in the body wall and neural tube, but the most striking feature was the duplication of the hindlimbs. When I showed the mutant to Moises, my supervisor, he said it was one of the most striking phenotypes that he had ever seen in his lab. Of course, we were curious to know how knocking out the Tgf-beta receptor led to the formation of additional hindlimbs. By then, I was already two years into my PhD, but the excitement around this finding made us pivot the project, and I had to learn a lot about limb development.

Limbs and genitalia share more than we think

To understand the phenotype first we characterized the expression patterns of limb regulatory genes at midgestational stages during early limb bud development. Interestingly, we observed that the hindlimb field in the mutants was extended posteriorly, almost reaching the genital area. The genital primordium, in turn, was underdeveloped in the mutants. This reduction in genital growth could either coincide with hindlimb duplication due to independent regulation of the two structures by Tgfbr1, or alternatively, result from the recruitment of the genital primordium into the limb field, resulting in its development into an additional set of hindlimbs. Hindlimbs and external genitalia precursors are both induced at the trunk to tail transition and, despite developing into morphologically very different appendages, share many regulatory genes [7], [8]. The commonalities between hindlimb and genitalia development prompted us to explore the latter hypothesis. We tried to recreate the activation of limb genes in the pericloacal mesenchyme (the precursor of external genitalia) by overexpression. After generating several transgenics expressing early limb specific genes in the pericloacal mesenchyme, we found that the misexpression of a single gene was insufficient to recapitulate mutant phenotype. We decided to change our approach and focus on the general mechanisms of tissue response. Given that hindlimbs and external genitalia share the expression of so many genes, how are their developmental outcomes so different?

Tgfbr1 guides tissue response by acting on chromatin state

To answer this question, we decided to look at the cis-regulatory regions in the two structures in wild type embryos and Tgfbr1 conditional knock out (cKO). The simplest way to evaluate the activity of the chromatin regions is determining whether they are compacted into nucleosome (inactive) or are nucleosome-free (accessible for transcription factors). We used ATAC-seq, which only generates sequences of open, nucleosome-free chromatin regions [9]. This analysis identified a set of genital-specific regulatory regions that lost accessibility in mutant tissue collected from genital area. The loss of accessibility in these regions could contribute to the inability to activate expression of genes required for genital growth, despite the presence of upstream transcription factors. Further analysis of the mutant extra hindlimb showed that it shared more features with genital samples than with wild type limbs, in line with the hypothesis of its genital origin. Despite that, some chromatin regions in the extra hindlimb acquired limb-type patterns. We believe that gained accessibility in the limb specific regulatory regions of the mutant genital area contributed to its development into an ectopic limb.

Of course, not every nucleosome-free chromatin region is a regulatory region. To validate our findings, we tested several potential regulatory regions using a transgenic reporter assay. To narrow the search, we focused on regions near genes known to be involved in development of limbs and external genitalia. Another criterion for identifying potential regulatory regions was evolutionary conservation. In that way, we identified several regions that drive reporter expression in the genital tubercle (GT) among those that lost accessibility in mutant genital area.

One of the most interesting changes in chromatin was found in a well characterized enhancer driving Gremlin expression in the limb. Gremlin, a secreted Bmp inhibitor, is expressed in response to Sonic Hedgehog (Shh) [10]. Both genes are required for proper limb development [11], [12]. Shh is also a driver of genital growth [13]. However, Gremlin is not expressed in the developing genitalia, despite the presence of Shh signaling. Our results indicate that in wild type genitalia, Gremlin enhancers are inaccessible to Shh regulatory activity. In contrast, in Tgfbr1 cKO embryos, one of the Gremlin enhancers is accessible, leading to ectopic Gremlin activation in the pericloacal mesenchyme. Another regulatory region that we examined in more detail was associated with GT growth and contained binding sequences for the Wnt downstream transcription factor Lef1. By generating sequential deletions of Lef1 binding sequences, we showed that reducing their number decreases reporter activity in the GT. These results illustrate how Tgfbr1 modulates response of limb and genital precursor tissues to common regulatory factors, particularly signaling pathways. This explains how loss of Tgfbr1 leads to a systemic shift in pericloacal mesenchyme response, uncovering its potential to form limbs.

Concluding remarks

The interesting phenotype of our mutant, and (I hope) the novelty of the mechanism we discovered brought a lot of attention to our preprint. Although the manuscript was rejected by two journals, it finally found its place in Nature Communications, which was immensely gratifying. I am very grateful to the reviewers for their comments and suggestions that helped us improve the manuscript.

Unexpectedly for me, the published work received a lot of media attention, likely due to the extraordinary phenotype of the Tgfbr1 cKO. While it was exciting to see my work getting attention, it made me think about the importance of science communication, especially when working with animal models, and even more when conducting basic research. The lack of direct medical application in our research made some people question the justification of our work. This experience underscored the need for clear and effective communication to convey the value and purpose of scientific research to the public.

References

[1]           A. C. Mcpherron, A. M. Lawler, and S. Lee, ‘Regulation of anterior / posterior patterning of the axial skeleton by growth / differentiation factor 11’, Nature, vol. 22, no. july, pp. 1–5, 1999.

[2]           A. C. McPherron, T. V. Huynh, and S. J. Lee, ‘Redundancy of myostatin and growth/differentiation factor 11 function’, BMC Dev. Biol., vol. 9, no. 1, pp. 1–9, 2009, doi: 10.1186/1471-213X-9-24.

[3]           O. Andersson, E. Reissmann, and C. F. Ibáñez, ‘Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis.’, EMBO Rep., vol. 7, no. 8, pp. 831–7, 2006, doi: 10.1038/sj.embor.7400752.

[4]           A. D. Jurberg, R. Aires, I. Varela-Lasheras, A. Nóvoa, and M. Mallo, ‘Switching axial progenitors from producing trunk to tail tissues in vertebrate embryos’, Dev. Cell, vol. 25, no. 5, pp. 451–462, 2013, doi: 10.1016/j.devcel.2013.05.009.

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(1 votes)
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We are looking for a motivated, talented and energetic PhD student to join our lab under the supervision of Dr. Benedetta Artegiani and Dr. Delilah Hendriks.

Our lab has expertise and interest in liver and brain biology and their associated diseases.

To this end, in the past years, we have developed 3D human organoid culture systems to grow mini-livers and mini-brains in a dish. We use these models together with state-of-the-art technologies such as for instance CRISPR-Cas9, to model different diseases, such as cancer and genetic disease, and to understand mechanisms underlining the pathogenesis as well as regulating proper organ development.

This PhD position is fully funded (4-years) by a recent grant from the Dutch cancer society (KWF). This project will deal with understanding how chronic liver disease develops into cancer. To read more about the project, visit the link below:

https://www.kwf.nl/nieuws/toekenningen-call-2024-1

To read more about our lab, please visit:

https://www.bendellab.com

An official post to apply will be opened soon on the institutional webpage, but for informal inquiries we appreciate if you can reach out to us both in a joint email, and reviewing of interesting candidates can start earlier:

Benedetta Artegiani: b.a.artegiani@prinsesmaximacentrum.nl

Delilah Hendriks: d.f.g.hendriks-7@prinsesmaximacentrum.nl

(11 votes)
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On 19 June 2024, Development’s Editor James Wells (Cincinnati Children’s Hospital Medical Center) hosted a Development presents… webinar with three early-career researchers studying mechanics and morphogenesis. Catch up on the recordings of the talks.

Clémentine Villeneuve (Max Planck Institute for Molecular Biomedicine)

Louis Prahl (University of Pennsylvania)

Kyojiro Ikeda (University of Vienna)

(2 votes)
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