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

The preprints this month are hosted on bioRxiv – 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
• Environment, evolution and development

Cell Biology

Modelling

Tools & Resources

Research practice and education

Developmental biology

| Patterning & signalling

Evi1 is necessary for late activation of delta-notch signaling in sea urchin embryos

Sanjana Anand, Dr. David McClay

Axial Nephron Fate Switching Demonstrates a Plastic System Tunable on Demand

MaryAnne A. Achieng, Jack Schnell, Connor C. Fausto, Réka L. Csipán, Matthew E. Thornton, Brendan H. Grubbs, Nils O. Lindström

Stimulatory and inhibitory G-protein signaling relays drive cAMP accumulation for timely metamorphosis in the chordate Ciona

Akiko Hozumi, Nozomu M. Totsuka, Arata Onodera, Yanbin Wang, Mayuko Hamada, Akira Shiraishi, Honoo Satake, Takeo Horie, Kohji Hotta, Yasunori Sasakura

Neural crest cell derived DKK1 modulates Wnt signalling in the second heart field to orchestrate cardiac outflow tract development

Sophie Wiszniak, Dimuthu Alankarage, Iman Lohraseb, Ceilidh Marchant, Genevieve Secker, Wendy Parker, John Toubia, Melissa White, Sandra Piltz, Markus Tondl, Eleni Giannoulatou, David Winlaw, Gillian M. Blue, Congenital Heart Disease Synergy Group, Patrick P. L. Tam, Paul Thomas, Natasha Harvey, Sally L. Dunwoodie, Quenten Schwarz

A conserved differentiation program facilitates inhibitory neuron production in the developing mouse and human cerebellum

Jens Bager Christensen, Alex P.A. Donovan, Marzieh Moradi, Giada Vanacore, Mohab Helmy, Adam J. Reid, Jimmy Tsz Hang Lee, Omer Ali Bayraktar, Andrea H. Brand, N. Sumru Bayin

Wnt/β-catenin signalling assists cell fate decision making in the early mouse embryo

Joaquin Lilao-Garzon, Elena Corujo-Simon, Meritxell Vinyoles, Sabine C Fischer, Jose Guillen, Tina Balayo, Silvia Munoz-Descalzo

Cranial suture integrity is maintained by Fgfr3 in zebrafish

Rachel Pereur, Yvan Marc, Yuliya Lim, Alain Schmitt, Marilyne Malbouyres, Anatole Chessel, Florence Ruggiero, Marie-Claire Schanne-Klein, Laurence Legeai-Mallet, Emilie Dambroise

PROX1 Controls Cellular Patterning, Innervation and Differentiation in the Mouse Organ of Corti

Shubham Kale, Dimitri Traenkner, Ellison J. Goodrich, Satish R. Ghimire, Thomas M. Coate, Michael R. Deans

Dorsoventral limb patterning in paired appendages emerged via regulatory repurposing of an ancestral posterior fin module

Sofía Zdral, Simone Giulio Bordignon, Axel Meyer, Marian A. Ros, Joost M. Woltering

Purinergic signalling and calcium dynamics: potential drivers in the onset of coordinated intestinal motility in human fetal development

Benjamin Jevans, Atchariya Chanpong, Luca Peruzza, Silvia Perin, Ben Cairns, Parth Tagdiwala, Pieter Vanden Berghe, Grant W Hennig, Conor J McCann

Dpp Scaling is Not the Key to Robust Wing Patterning in Drosophila

Bhagyashree A. Ghag, Alexander W. Shingleton

Interactions between the Bone Morphogenetic Protein and the Planar Cell Polarity Pathways lead to distinctive ethanol-induced facial defects

Raèden Gray, Anna Llyod, C. Ben Lovely

SoxB1 family members inhibit Wnt signaling to promote maturation and deposition of stable neuromasts by the zebrafish Posterior Lateral Line primordium

Greg Palardy, Kyeong-won Yoo, Sana Fatma, Abhishek Mukherjee, Chongmin Wang, Priyanka Ravi, Ajay B Chitnis

| Morphogenesis & mechanics

Mechanical Stress dissipation in locally folded epithelia is orchestrated by calcium waves and nuclear tension changes

Marvin Brun-Cosme-Bruny, Lydia Pernet, Kenny Elias, Christophe Guilluy, Christiane Oddou, Monika Elzbieta Dolega

The microtubule-binding protein EML3 is required for mammalian embryonic growth and cerebral cortical development; Eml3 null mice are a model of cobblestone brain malformation

Isabelle Carrier, Eduardo Diez, Valerio E.C. Piscopo, Susanne Bechstedt, Hans van Bokhoven, Myriam Srour, Albert Berghuis, Stefano Stifani, Yojiro Yamanaka, Roderick R. McInnes

Tissue spreading couples gastrulation through extracellular matrix remodelling in early avian embryos

Lakshmi Balasubramaniam, Venus Sin Yiu Ho, Filomena Gallo, Karin Müller, Fengzhu Xiong

Non-uniform temporal scaling of neurogenesis for species-specific dosing of cortical excitatory subtypes

Yuki Yamauchi, Xuanhao D. Zhou, Rafat Tarfder, Pauline Rouillard, Merve Bilgic, Shuto Deguchi, Tomonori Nakamura, Yusuke Kishi, Kazuo Emoto, Ikuo K. Suzuki

Spatial patterning of contractility by a mechanogen gradient underlies Drosophila gastrulation

Gayatri Mundhe, Valentin Dunsing-Eichenauer, Jean-Marc Philippe, Élise Da Silva, Claudio Collinet, Thomas Lecuit

The identification and characterization of hillocks in the postnatal mouse and human airway

Yohana Otto, Gergana Shipkovenska, Qiaozhen Liu, Jiawei Sun, Lida P. Hariri, Viral S. Shah, Jayaraj Rajagopal

Mechanics regulate the postembryonic developmental maturation and function of sensory neurons in a pre-vertebrate chordate

Andreas Midlang, Carl Matthew Jones, Luc Seegers, Jorgen Hoyer, Sigurd Glørstad, Marios Chatzigeorgiou

Intestinal Tissue Mechanics Regulate Angiogenesis and Stem Cell Proliferation via Vascular Piezo

Jade A. Phillips, Jessica Perochon, Cai T. Johnson, Matthew Walker, Colin Nixon, Mark Hughes, André Barros-Carvalho, Yachuan Yu, Louise Mitchell, Karen Blyth, Massimo Vassalli, Julia B. Cordero

Spatially organized cellular communities shape functional tissue architecture in the pancreas

Alejo Torres-Cano, Jean-Francois Darrigrand, Gabriel Herrera-Oropeza, Georgina Goss, David Willnow, Anna Salowka, Debashish Chitnis, Morgane Rouault, Alessandra Vigilante, Francesca M. Spagnoli

Inverted Assembly of the Lens Within Ocular Organoids Reveals Alternate Paths to Ocular Morphogenesis

Elin Stahl, Miguel Angel Delgado-Toscano, Ishwariya Saravanan, Anastasija Paneva, Joachim Wittbrodt, Lucie Zilova

Cranial suture integrity is maintained by Fgfr3 in zebrafish

Rachel Pereur, Yvan Marc, Yuliya Lim, Alain Schmitt, Marilyne Malbouyres, Anatole Chessel, Florence Ruggiero, Marie-Claire Schanne-Klein, Laurence Legeai-Mallet, Emilie Dambroise

Characterisation of spinal ligaments in the embryonic chick

Sarah Hennigan, Ebru Talak Basturkmen, Rebecca A. Rolfe

Integrin promotes basement membrane crossing and branching of an invading intracellular tube

Lauren N. Meyer, Michael Hertel, Jeremy Nance

The V-ATPase/ATG16L1 axis drives membrane remodeling during epithelial morphogenesis

Gabriel Baonza, Tatiana Alfonso-Pérez, Gonzalo Herranz, Carlos Quintana-Quintana, Carmen Gordillo-Vázquez, Yara El Mazjoub, L.M. Escudero, David G. Míguez, Elisa Martí, Nuria Martínez-Martín, Fernando Martín-Belmonte

| Genes & genomes

AGO2 slicing of a domesticated retrotransposon is necessary for normal vasculature development

Manish Kumar, Andrea G. Maria, Mahendra Prajapat, Joana A. Vidigal

AMPK modulates a DEAH Box RNA-helicase to attenuate TOR signaling and establish developmental quiescence

Sabih Rashid, Richard Roy

Morphogen-driven melanin pathway dynamics regulated by Wnt1 and apontic-like underlie larval spot coloration in Bombyx mori

Shinichi Yoda

The functional organization of chromosome territories in single nuclei during zygotic genome activation

Akshada Shankar Ganesh, Taylor M. Orban, Romir Raj, Peter I. Fatzinger, Anna Johnson, Sean M. Riccard, Akhmed Zhanaidarov, Mayu Inaba, Jelena Erceg

Haploinsufficiency of eNOS mitigates beneficial effects of maternal exercise on fetal heart development during pregestational diabetes

Ryleigh Van Neck, Xiangru Lu, Lambertus J. Wisse, Marco C. DeRuiter, Qingping Feng

Genetic compensation in podocalyxin-like mutants during zebrafish liver development

Alexis N. Ross, Natalie M. Miscik, Sharanya Maanasi Kalasekar, James D. Harris, Mimi Tran, Aavrati Saxena, Steven Andrew Baker, Kimberley Jane Evason

Spatial Transcriptomics Unveils the Blueprint of Mammalian Lung Development

Mingyue Chen, Junjie Lv, Qiao Zhang, Qian Gong, Ting Zhao, Zhenping Chen, Haishen Xu, Nan Zhou, Shan Jiang, Jian Du, Xuepeng Chen, Yuwen Ke

Functional genomics analysis of developing zebrafish and human endoderm reveals highly conserved cis-regulatory modules controlling vertebrate organogenesis

Daniela M. Figiel, Randa Elsayed, Mark D. Walsh, Simaran Johal, Ying Lin, Till Bretschneider, Sascha Ott, Andrew C. Nelson

Unilateral loss of recql4 function in Xenopus laevis tadpoles leads to ipsilateral ablation of the forelimb, hypoplastic Meckel’s cartilage and vascular defects

Caroline W. Beck, Matthew Reily-Bell, Louise S. Bicknell

Unraveling Enteroendocrine Cell lineage dynamics and associated gene regulatory networks during intestinal development

Sara Jiménez, Florence Blot, Aline Meunier, Valérie Schreiber, Colette Giethlen, Sabitri Ghimire, Maxime Mahe, Nacho Molina, Adèle De Arcangelis, Gérard Gradwohl

Loss of cep57 function induces G1 arrest and microcephaly

Sharada Iyer, Advait Gokhale, Pooja Shree Murugesan, Megha Kumar

DNA Methylation in Sex Chromosomes and Genes under Selection Underpins the Emergence of Sexual Size Dimorphism

Qian Wang, Xiancai Hao, Dafni Anastasiadi, Kaiqiang Liu, Shuo Li, Bo Feng, Rui Wang, Michael G. Ritchie, Yuyan Liu, Hong-Yan Wang, Lili Tang, Francesc Piferrer, Changwei Shao

Deciphering of single-cell chromatin accessibility and transcriptome reveals the discrepancy for ex vivo human erythropoiesis

Zijuan Xin, Wei Zhang, Lijuan Zhang, Guangmin Zheng, Tingting Jin, Meng Li, Yangliu Shao, Liping Dou, Shengwen Huang, Zhaojun Zhang, Xiangdong Fang

Psmd13, a proteosome regulatory subunit identified in miR-29a regulation during neurogenesis

Diji Kuriakose, Grant Morahan, Zhicheng Xiao

Analysis of 14q12 microdeletions reveals novel regulatory loci for the neurodevelopmental disorder-related gene, FOXG1

Aishwarya Ramamurthy, Masha D Bandouil, Likhita Aluru, Esther Yoon, Nicholas Bodkin, Jennifer Z Cheng, Carina G Biar, Jeffrey D Calhoun, Gemma L Carvill

ISLET-1 knockdown causes abnormal peripheral axonal growth of mesencephalic trigeminal neurones in the chick embryo

Efstathia Artemis Koumoundourou, Sinziana Pop, Anthony Graham, Andrea Wizenmann

The role of m6A RNA methylation in the maintenance of X-chromosome inactivation and X to autosome dosage compensation in early embryonic lineages

Hemant C Naik, Runumi Baro, Amritesh Sarkar, M Muralidhar Nayak, Kartik Sunagar, Srimonta Gayen

In vivo CRISPR screening identifies regulators of hyperplastic and hypertrophic adipose remodelling in zebrafish

Rebecca Wafer, Panna Tandon, James E. N. Minchin

NSD2 links developmental plasticity to mitochondrial function in muscle and lymphocyte differentiation

Jorge Martínez-Cano, Ana Sagrera, Belén S. Estrada, Sara Cogliati, Nuria Martínez-Martín, César Cobaleda

Life-cycle-related gene expression patterns in the brown algae

Pelagie Ratchinski, Olivier Godfroy, Benjamin Noel, Jean-Marc Aury, J. Mark Cock

Tulp3 quantitative alleles titrate requirements for viability, brain development, and kidney homeostasis but do not suppress Zfp423 mutations in mice.

Corinne A. McCoy, Dorothy Concepcion, Mark G. Mezody, Raquel Z. Lara, Ojas Deshpande, Catherine Liang, Renee Long, Bruce Alan Hamilton

VGLL1 contributes to both the transcriptome and epigenome of the developing trophoblast compartment

Ruben I Calderon, Nirvay Sah, Molly Huang, Ryan H. Kittle, Walee Shaik, Jennifer N Chousal, Sampada Kallol, Tony Bui, Robert Morey, Alejandra Mitre, Norah M.E. Fogarty, Claudia Gerri, Claire Zheng, Peter ME DeHoff, Pratik Home, Kathy Niakan, Heidi Cook-Andersen, Kathleen M. Fisch, Soumen Paul, Francesca Soncin

A Y-linked duplication of anti-Mullerian hormone is the sex determination gene in threespine stickleback

Matthew J Treaster, Jenny McCann, Kyra S Solovei, Ryan J Palmieri, Michael A White

| Stem cells, regeneration & disease modelling

Immune surveillance and pruning of neuronal stem cells in the medaka retina

Rashi Agarwal, Joergen Benjaminsen, Katharina Lust, Clara Becker, Natalia Fuchs, Eva Hasel de Carvalho, Fanny Eggeler, Omnia El Said Ibrahim, Narges Aghaallaei, Baubak Bajoghli, Joachim Wittbrodt

The essential role of connective-tissue cells during axolotl limb regeneration

Damián García-García, Dunja Knapp, Minjoo Kim, Katelyn Jamwal, Heath Fuqua, Ryan P. Seaman, Riley E. Grindle, Sergej Nowoshilow, Maria Novatchkova, Fred W. Kolling, Joel H. Graber, Prayag Murawala

Excessive chondrogenesis in the blastema initiates during hypomorphic limb regeneration in Xenopus froglet, but not during patterned limb regeneration in Xenopus tadpoles and newts

Suzu Kobari, Hibiki Yokoyama, Kagayaki Kato, Rina Sato, Nana Kitagawa, Joe Sakamoto, Yasuhiro Kamei, Hitoshi Yokoyama

Canonical Wnt/β-catenin signalling regulates inducible aging and regeneration loss in hydra

Jácint Tökölyi, Yukino Kumagai, Regina Krisztina Szilágyi, Nikoletta Andrea Nagy, Virág Szakál, Retno Novvitasari Hery Daryono

Designed Soluble Notch Agonist Drives Human Ameloblast Maturation for Tooth Regeneration

Anjali P. Patni, Rubul Mout, Rachel Moore, Ammar Alghadeer, George Q Daley, David Baker, Julie Mathieu, Hannele Ruohola-Baker

The integration mechanism of the four positional cues—anterior, posterior, dorsal, and ventral—in axolotl limb regeneration

Sakiya Yamamoto, Saya Furukawa, Ayaka Ohashi, Mayuko Hamada, Akira Satoh

Modular regulation of the stem cell transcriptome defines self-renewal, differentiation, and dedifferentiation

Amelie Raz, Hafidh Hassan, Yukiko Yamashita

Multiple cis-regulatory elements collaborate to control mdka expression in zebrafish adult telencephalic neural stem cells during constitutive and regenerative neurogenesis

Jincan Chen, Agnes Hendriks, Masanari Takamiya, Tanja Beil, Nicolas Diotel, Sepand Rastegar

Retinoic acid signaling alters the balance of epidermal stem cell populations in the skin

Thisakorn Dumrongphuttidecha, Mizuho Ishikawa, Nina Cabezas-Wallscheid, Aiko Sada

An intercellular metabolic relay for brain sparing in Drosophila

Adrien Franchet, Yuhong Jin, Clare L. Newell, Victor Girard, Gérard Manière, Yaël Grosjean, Christopher Barrington, James I. MacRae, Ian S. Gilmore, Alex P. Gould

Aberrant formation of long-range projections across different neurodevelopmental disorders converges on molecular and cellular nexuses

Federica Furlanetto, Alejandro Segura, Mathar Kravikass, Pritha Dolai, Sarah Frank, Sören Turan, Angelica Luna Leal, Stephan Käseberg, Susann Schweiger, Chichung D. Lie, Vasily Zaburdaev, Marisa Karow, Sven Falk

FGF overactivation underlies reduced neurogenesis in cerebellar organoid models of neurodevelopmental ciliopathy

Ludovica Brunetti, Antonia Wiegering, Isabelle Anselme, Lidia Pollara, Martin Catala, Christophe Antoniewski, Enza Maria Valente, Sylvie Schneider-Maunoury, Christine Vesque

Pluripotent Stem Cell Plasticity is Sculpted by a Slit-Independent Robo Pathway in a Regenerative Animal

Kuang-Tse Wang, Yu-Chia Chen, Fu-Yu Tsai, Catherine P Judy, Carolyn E Adler

Autophagy-Dependent Regulation of YAP1 by STK38 Governs Recruitment of Differentiated Cells as Progenitor Cells During Regeneration

Yongji Zeng, Yang-Zhe Huang, Qing Kay Li, Raymond Ho, Steven J. Bark, Spencer G. Willet, Jason C. Mills

Tumour-derived Ilp8 and Upd3 control intestinal progenitor cells depletion during cachexia in Drosophila larvae

Jennifer Falconi, Miriam Rodríguez-Vázquez, Katrin Strobel, Céline Jahannault-Talignani, Lisa Heron-Milhavet, Patrice Lassus, Charles Géminard, Alexandre Djiane

Muc6-expressing gastric isthmus progenitors contribute to regeneration and metaplasia supported by myeloid-mesenchymal interactions

Junya Arai, Yusuke Iwata, Ayumu Tsubosaka, Hiroto Kinoshita, Shintaro Shinohara, Sohei Abe, Toshiro Shiokawa, Katsuyuki Oura, Nobumi Suzuki, Masahiro Hata, Ken Kurokawa, Yukiko Oya, Mayo Tsuboi, Sozaburo Ihara, Keita Murakami, Chihiro Shiomi, Chie Uekura, Hiroaki Fujiwara, Hiroaki Tateno, Seiya Mizuno, Satoru Takahashi, Yutaka Suzuki, Akinori Kanai, Tetsuo Ushiku, Hideaki Ijichi, Yoshihiro Hirata, Masato Kasuga, Valerie P. O’Brien, Nina Salama, Miwako Kakiuchi, Shumpei Ishikawa, Timothy C. Wang, Yoku Hayakawa, Mitsuhiro Fujishiro

Somites are a source of nephron progenitors in zebrafish

Zhenzhen Peng, Thitinee Vanichapol, Phong Dang Nguyen, Hao-Han George Chang, Katrinka M. Kocha, Lori L. O’Brien, Peter D. Currie, Peng Huang, Alan J. Davidson

Macrophages Mediate Antiviral Immunity and Repair of Type 2 Alveolar Epithelial Cells in a Human Stem Cell Model

Declan L. Turner, Hannah Baric, Katelyn Patatsos, Sahel Amoozadeh, Michael See, Kathleen A. Strumila, Jack T. Murphy, Liam Gubbels, Elizabeth Ng, Andrew Elefanty, Melanie Neeland, Shivanthan Shanthikumar, Sarah L. Londrigan, Mirana Ramialison, Fernando J. Rossello, Ed Stanley, Rhiannon B. Werder

Tnfrsf10 Signaling is Required to Maintain the Stem Cell Niche in the Zebrafish Lateral Line

Chunxin Fan, Xiaoyi Yuan, Jian Wang, Wuhong Pei, Hongfei Zheng, Xinyu Zhang, Shawn M. Burgess

Tissue scarring provides a biomechanical framework to promote mammalian bile duct regeneration through the activation of integrin-SRC/FAK signalling

Alexander Walker, Paula Olaizola, Euan Brennan, Edward J Jarman, Yuelin Yao, Elizabeth Carmichael, Andreea Gradinaru, Alexander EP Loftus, David H Wilson, Anabel Martinez Lyons, Laura Charlton, Kimberley Ober-Vliegen, Wunan Mi, Amy Broeders, Kyle Davies, Neil O. Carragher, Asier Unciti-Broceta, Timothy J Kendall, Luc van der Laan, Monique MA Verstegen, Margaret C Frame, Scott H Waddell, Luke Boulter

Planar cell polarity signaling controls cell division symmetry to promote termination of adult tissue regeneration

Samantha J. Hack, Wendy S. Beane

Absence of a prolonged macrophage and B cell response inhibits heart regeneration in the Mexican cavefish

Esra Sengul, Helen G. Potts, William T. Stockdale, Ryan D. Carter, Laura Bevan, Maria Nozdrina, Rita Alonaizan, Zhilian Hu, Abigail Goodship, Jun Ying, Konstantinos Lekkos, Lucy O’Byrne, Madeleine E. Lemieux, Rebecca Richardson, Mathilda T.M. Mommersteeg

| Plant development

The minimal cell-cycle control system in Marchantia as a framework for understanding plant cell proliferation

Facundo Romani, Ignacy Bonter, Marius Rebmann, Go Takahashi, Fernando Guzman-Chavez, Francesco De Batté, Yuki Hirakawa, Jim Haseloff

ALFIN-LIKE Proteins Orchestrate H3K4me3-H3K27me3 Crosstalk to Regulate Plant Embryogenesis

Janik Scotton, Yixuan Fu, Edouard Tourdot, Marc W Schmid, Sara Simonini

A network of RS splicing regulatory proteins controls light-dependent splicing and seedling development

Jennifer Saile, Hannah Walter, Moritz Denecke, Patrick Lederer, Laura Schütz, Andreas Hiltbrunner, Katharina Lepp, Sofia Lobato-Gil, Petra Beli, Andreas Wachter

ROS regulation of stigma papillae growth and maturation in Arabidopsis thaliana

Subramanian Sankaranarayanan, Sowmiya Devi Venkatesan, Thomas C. Davis, Sharon A. Kessler

STM is required for fate establishment of productive shoot progenitor cells in Arabidopsis tissue culture

Ning Zhai, Dixiang Xie, Lin Xu

Expression levels of the Band-7 protein FLOTILLIN modulate salt tolerance, growth and development in the moss Physcomitrium patens

Erika Csicsely, Norina Noor, Susanne Mühlbauer, Hans-Henning Kunz, Serena Schwenkert, Martin Lehmann, Andreas Klingl, Oguz Top, Wolfgang Frank

SlHSFB3a developmentally regulates lateral root formation by modulating auxin signaling in tomato

Adity Majee, Babythoithoi Sairem, Vinod Kumar, Aniruddha P. Sane, Vidhu A. Sane

INDETERMINATE DOMAIN-DELLA protein interactions orchestrate gibberellin-mediated cell elongation in wheat and barley

Patrycja Sokolowska, Matthias Jost, Wolfram Buss, Brett Ford, Peter Michael Chandler, Wolfgang Spielmeyer, Andy Phillips, Alison K. Huttly, Danuše Tarkowská, Rocío Alarcón-Reverte, Suzanne J. Clark, Stephen Pearce, Peter Hedden, Stephen G. Thomas

GPAT2 plays a role in the root cap cuticle formation of Arabidopsis that is not redundant to GPAT4 and GPAT8

Alice Berhin, Aurore Guerault, Damien De Bellis, Christiane Nawrath

A citrullination-ubiquitination pathway controls pre-meiotic H1 eviction and is essential for gametogenesis in Arabidopsis

Yanru Li, Danli Fei, Jasmin Schubert, Kinga Rutowicz, Zuzanna Kaczmarska, Alberto Linares, Alejandro Giraldo-Fonseca, Sylvain Bischof, Ueli Grossniklaus, Celia Baroux

Analysing the Role of KIN10 in Directional Root Growth Regulation in Arabidopsis thaliana

Katarzyna Retzer, Judith Garcia-Gonzalez, Karel Muller, Jozef Lacek, Simon Pree, Nathalie Friedl, Wolfram Weckwerth

A transcriptional atlas of early Arabidopsis seed development suggests mechanisms for inter-tissue coordination

Caroline A Martin, Kylee R Cogdill, Alesandra L Pusey, Mary Gehring

From Genes to Glands: Unraveling the Pivotal Influence of NtAGL66, an AGAMOUS-like Transcription Factor, on Glandular Trichome Development in Nicotiana tabacum

Alice Berhin, Gabriel Walckiers, Manon Peeters, Belkacem El Amraoui, Charles Hachez

| Environment, evolution and development

Teeth Outside the Jaw: Evolution and Development of the Toothed Head Clasper in Chimaeras

Karly E. Cohen, Michael I. Coates, Gareth J. Fraser

Developmental stages of Arthroleptella villiersi (Pyxicephalidae)

Susan Schweiger, Benjamin Naumann, Hendrik Müller

Evolution of the olfactory system during the radiation of Heliconiini butterflies

Yi Peng Toh, Francesco Cicconardi, Giorgio Bianchini, Richard M Merrill, Stephen H. Montgomery

Correlated evolution of the neck, head and forelimb across the theropod-bird transition

Ryan D. Marek, Ryan N. Felice

Pleiotropy accelerates tooth phenotypic and genomic evolution — An in silico study under the lens of development

Pascal Felix Hagolani, Marie Sémon, Guillaume Beslon, Sophie Pantalacci

Whole-mount acetylcholinesterase (AChE) staining reveals unique motor innervation of the lamprey oral region: with special reference to the evolutionary origin of the vertebrate jaw

Motoki Tamura, Daichi G. Suzuki

Pollen Diet and Sterol Provisioning Differentially Affected Larval Development in a Generalist Solitary Bee

Carlos Martel, Josef Kreidt, Samuel Furse, Jennifer Scott, Janine Griffiths-Lee, Geraldine A. Wright, Philip C. Stevenson

Theoretical origins of extreme cell differentiation irreversibility: a dynamic model of organismal size effects

Yuanxiao Gao, Xueyan Zhao, Caixia Li

From head to tail: does habitat use drive morphological variation in snakes?

David Hudry, Anthony Herrel

Brain dopamine imbalance causes follicle death and underlies negative effect of high sugar diet during Drosophila oogenesis

Rodrigo Dutra Nunes, Daniela Drummond-Barbosa

Cell Biology

The developing retina undergoes mitochondrial remodeling via PINK1/PRKN-dependent mitophagy

Juan Zapata-Muñoz, Juan Ignacio Jiménez-Loygorri, Michael Stumpe, Beatriz Villarejo-Zori, Sandra Alonso-Gil, Petra Terešak, Benan J. Mathai, Ian G Ganley, Anne Simonsen, Jörn Dengjel, Patricia Boya

A human cytotrophoblast-villous endothelium-fetal organ multi-cell model and the impact on gene and protein expression in placenta cytotrophoblast, fetal hepatocytes and fetal kidney epithelial cells

Helen N. Jones, Rebecca L. Wilson

Nanosecond pulsed electric field precisely manipulates cytoplasmic Ca2+ oscillations during oocyte activation

Yi-Dan Sun, Tong An, Rong Liang, Yu-Wen Luo, Hong-Ze Xia, Lei Fu, Shuo Han, Yi-Xiao Zhu, Zi-Yi Song, Xue-Yan Bai, Yao Fu, Xiang-Wei Fu, Yun-Peng Hou, Qun Lu

BCAS2 promotes primitive hematopoiesis by sequestering β-catenin within the nucleus

Guozhu Ning, Yu Lin, Haixia Ma, Jiaqi Zhang, Liping Yang, Zhengyu Liu, Lei Li, Xinyu He, Qiang Wang

Attenuation of mosaic aneuploidy and erroneous first mitotic division of human embryos

Cerys E. Currie, Aleksandra Byrska, Deborah M. Taylor, Muriel Erent, Daniela Bakalova, Xuhui Sun, Constandina Koki, Nigel J. Burroughs, Richard. A. Anderson, Adele L. Marston, Geraldine M. Hartshorne, Andrew D. McAinsh

Direct visualization and tracing of DNA fold in Drosophila embryo

Fadwa Fatmaoui, Pascal Carrivain, Fatima Taiki, Diana Grewe, Wim Hagen, Burkhard Jakob, Jean-Marc Victor, Amélie Leforestier, Mikhail Eltsov

4D mitochondrial network assumes distinct and predictive phenotypes through human lung and intestinal epithelial development

Gillian McMahon, Dhruv Agarwal, Mehul Arora, Zichen Wang, Hiroyuki Hakozaki, Johannes Schöneberg

A Role for Importin α in Ciliogenesis and Cilia Length Regulation during Nephrogenesis

Natalie Mosqueda, Patrick James Sutton, Christopher William Brownlee

FGF-dependent, polarized SOS activity orchestrates directed migration of C. elegans muscle progenitors independently of canonical effectors in vivo

Theresa V Gibney, Jacob I Mardick, Neal R Rasmussen, Laila Latifi, Meera V Sundaram, David J Reiner, Ariel M Pani

Apical-basal polarity regulates Collagen IV-dependent cell-cell adhesion in the Drosophila adipose tissue

Jameela Almasoud, Cyril Andrieu, Bren Hunyi Lee, Anna Franz

Identification of N-acetyl-rich heparan sulfate binding motifs and their role in expanding BMP distribution and signaling by Cerberus

Takayoshi Yamamoto, Yusuke Mii, Hidetoshi Saiga, Tatsuo Michiue, Masanori Taira

Disruption of spindle orientation and protein localization during asymmetric cleavage by pharmacological inhibition of serotonin signaling

Ayaki Nakamoto, Lisa M. Nagy

Multivalent assembly of PAR-3 / aPKC complexes establishes cell polarity in C. elegans zygotes

Sheng-Ping Hsu, Daniel J. Dickinson

Ploidy and neuron size impact nervous system development and function in Xenopus

Xiao Liu, Christine Wan, Sara Aijaz Shah, Rebecca Heald

Amniotic fluid extracellular vesicle properties evolve with gestational age and reflect fetal development

Ishara Atukorala, Sally Beard, Ching-Seng Ang, Hamish Brown, Swetha Raghavan, Natasha de Alwis, Bianca Fato, Natalie Binder, Natalie Hannan, Lisa Hui

Signaling scaffold Shoc2 regulates lymphangiogenesis by suppressing mTORC1-mediated IFN responses

Patricia Wilson, Vishakha Vishwakarma, Rebecca Norcross, Kashmira Khaire, Van N. Pham, Brant M. Weinstein, Hyun Min Jung, Emilia Galperin

Modelling

Cell divisions both challenge and refine tissue boundaries in the Drosophila embryo

Veronica Castle, Merdeka Miles, Rodrigo Fernandez-Gonzalez, Gonca Erdemci-Tandogan

Curvature induced patterns: A geometric, analytical approach to understanding a mechanochemical model

Daphne Nesenberend, Arjen Doelman, Frits Veerman

Tools & Resources

Gene expression cartography of a developing neuronal structure

Leonardo Tadini, Lilia Younsi, Isabel Holguera, Felix Simon, Maximilien Courgeon, Nikos Konstantinides

Characterization of the intraspecies chimeric mouse brain at embryonic day 12.5

Phoebe Strell, Madison A. Waldron, Sether Johnson, Anala Shetty, Andrew T. Crane, Clifford J. Steer, Walter C. Low

Epiproteomic control of the epitranscriptome drives cortical neurogenesis

Ekaterina Borisova, Katherine J. Cuthill, Rike Dannenberg, Janina Koch, Julius Nowaczyk, Theres Schaub, Manuela Schwark, Nicolai Kastelic, Ivanna Kupryianchyk-Schultz, Marieluise Kirchner, Tancredi Massimo Pentimalli, Thornton J. Fokkens, Frank Stein, Carola Dietrich, Claudia Quedenau, Tatiana Borodina, David Schwefel, Thomas Conrad, Agnieszka Rybak-Wolf, Nikolaus Rajewsky, Philipp Mertins, Per Haberkant, Sonja Lorenz, Nils Brose, Hiroshi Kawabe, Victor Tarabykin, Mateusz C. Ambrozkiewicz

Anatomical and Molecular Characterization of the Zebrafish Meninges

Marina Venero Galanternik, Daniel Castranova, Ryan D. Gober, Tuyet Nguyen, Madeleine Kenton, Gennady Margolin, Aurora Kraus, Abhinav Sur, Louis E. Dye 3rd, Van Pham, Adilenne Maese, Melanie Holmgren, Aniket V. Gore, Bakary Samasa, Allison Goldstein, Andrew E. Davis, Avery A. Swearer, James Iben, Tianwei Li, Steven L. Coon, Ryan K. Dale, Jeffrey A. Farrell, Brant M. Weinstein

An optogenetic toolkit for robust activation of FGF, BMP, & Nodal signaling in zebrafish

Leanne E. Iannucci, Velanganni Selvaraj Maria Thomas, Micaela R. Murphy, Caitlin E.T. Donahue, William K. Anderson, Catherine E. Rogers, Allison J. Saul, Katherine W. Rogers

Identification and characterization of early human photoreceptor states and cell-state-specific retinoblastoma-related features

Dominic W.H. Shayler, Kevin Stachelek, Linda Cambier, Sunhye Lee, Jinlun Bai, Bhavana Bhat, Mark W. Reid, Daniel J. Weisenberger, Jennifer G. Aparicio, Yeha Kim, Mitali Singh, Maxwell Bay, Matthew E. Thornton, Eamon K. Doyle, Zachary Fouladian, Stephan G. Erberich, Brendan H. Grubbs, Michael A. Bonaguidi, Cheryl Mae Craft, Hardeep P. Singh, David Cobrinik

Embryonic Durotaxis: A Mechanical Framework for Understanding Cesarean Scar Pregnancy

Jialing Cao, Huanyu You, Jianwen Li, Shiping Yue, Bingqi Song, Hangyu Li, Jiyu Wei, Dongshi Guan, Yan Zu, Zheng Xu, Yan Wang, Yubo Fan, Jing Du

Research practice & education

Modeling human phenotypes in the nematode C. elegans during an undergraduate developmental biology course

Sireen Aburaide, Suad Ahmed, Mason Chamberlain, Yoskar Deleon, Ahmed Elewa, Allison Hookom, Evelyn Juen, Divine Katasi, Bobby Lee, Samantha Meyer, Luís Millan, Madeline Shaw, DJ Smith, Anthony Vassallo, Tashi Wangmo, Daniel Wolfson, Pader Xiong, Lian Yaeger, The Augsburg BIO474 Consortium

A systematic review of professional society-backed biology education DEI research: The groups, research methods, and levels of analyses comprising the field

Candice Idlebird, Rebecca Campbell-Montalvo, Gary S. McDowell, Emily Blosser, Richard Harvey, Jana Marcette

Deep Learning-Driven Gender Classification of Drosophila melanogaster: Advancing Real-Time Analysis with Mobile Integration

Jayant Rai, S Aswini, Soumyadeep Paul, Triveni Shelke, Ishaan Gupta

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To accompany the Biologists @ 100 conference, we’ve partnered with FocalPlane to bring to you an image competition. We shortlisted 15 images and asked you to vote for your favourite online and in person at the conference. On the final day of the conference, we announced the top3 images of the competition.

In this ‘Featured image’ post, we find out more about the story behind Özge Özgüç’s image, which was the winner of the competition.

What is your background?

I completed my undergraduate education in the Department of Molecular Biology and Genetics at Middle East Technical University (METU) in Ankara, Turkey. During this time, I participated in research across different fields of biology through various internships to discover what truly excited me. It was during one of these internships that I realized I was most interested in developmental biology.  To follow this interest, I pursued a master’s in Developmental Biology at Sorbonne University in Paris/France, followed by a PhD in Cellular and Developmental Biology at Institut Curie in Paris/France in the lab of Jean-Léon Maître. During my PhD, I focused on the physical forces that shape the preimplantation mouse embryo, particularly how actomyosin contractility prepare itself for morphogenesis by transitioning from an egg to an embryo state before it becomes the driving machinery behind the morphogenetic events of preimplantation development. Currently, I’m a postdoctoral researcher at the Institute for Bioengineering of Catalonia (IBEC) in Barcelona/Spain in the lab of Xavier Trepat. My work has grown increasingly interdisciplinary, bringing together developmental biology, biophysics, and bioengineering, to explore how mechanical forces influence early developmental processes across different model systems.

What are you currently working on?

Currently, I’m working on building experimental models that allow us to study the mechanical aspects of early human development. Human post-implantation stages are notoriously difficult to access and study in vivo, so we’re developing in vitro systems that recreate aspects of this development in a controlled and mechanically accessible way. With these tools, I aim to understand how physical forces, like pressure and tissue tension, influence key cell fate decisions and morphogenetic events, such as the symmetry breaking and start of gastrulation.

Can you tell us more about the story behind the image that you submitted to the image competition?

This image comes from a live-imaging session of micropatterned human induced pluripotent stem cells (hiPSCs), with fluorescent Lamin B marking the nuclear envelope. I was curious about how the cells were packing their nuclei into such a confined space, so I applied color code for the depth. Seeing nuclei at different height with a different color revealed the layered organization which was both informative and eye-catching. I first used the image as a cover slide for my lab meeting and got very nice comments about it, so I decided to submit it to the competition. The name “Cell-estial Bloom” actually came up while chatting with colleagues because we couldn’t decide whether it looked more like a flower or a galaxy.

What is your favourite technique?

I really enjoy live imaging. Something is very captivating about watching cells move and change shape in front of your own eyes and I find it incredibly satisfying to capture dynamic processes as they unfold. But I also love techniques that let you physically interact with cells and tissues. For example, during my PhD, I used various methods to change the cell size and shape, like aspirating them into micropipettes, fragmenting, fusing, or placing them into molds. These kinds of manipulations gave me a very hands-on understanding of how cells respond to mechanical cues. So, overall, I think I’m mostly excited by techniques that combine observation with gentle intervention, where you’re not just watching biology happen, but actively nudging it to reveal how it works.

What excites you the most in the field of developmental and stem cell biology?

What excites me the most is how the development of new tools and techniques open doors to explore developmental processes that once seemed out of reach. I love how these innovations often bring together ideas from completely different fields and invite you to look at the developmental processes from a fresh angle.

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The Node is turning 15 this year. If you’ve ever visited the Node to read, write and interact with the global developmental and stem cell biology community – thank you for your support!

We would really appreciate any feedback you have about the Node, to make sure the community site is still relevant and useful for you, our community members.

Please spare around 5 minutes to fill in our survey. Participants of the survey can enter a prize draw for a chance to win a bag of goodies from The Company of Biologists.

*The survey closes Monday 2 June 2025*

Thank you!

Joyce
Community Manager of the Node

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All the world’s a metabolic dance, early career scientists are leading the way!

Emerging perspectives in metabolism

This week, we delve into the story of Dr. Lianna W. Watt, a Leading Edge fellow and a postdoctoral researcher at Stanford University, who is passionate about unraveling the intricacies of metabolism and sex differences—one fly and mouse at a time. Driven by curiosity and a deep respect for basic science, Lianna has explored how diet can rewire the way male and female bodies store and break down fat. She’s worked across model systems—from Drosophila to mammals—always with an eye toward understanding how sex-specific metabolic regulation shapes health and disease. Keep reading to discover how mentorship, curiosity, and a few bags of mini eggs helped shape Lianna’s career—and why she believes that studying both sexes is fundamental biology, essential not only for understanding disease
and metabolism, but also for uncovering evolutionary principles. Check out all her work here .

What was your first introduction to the field of metabolism – what’s is your first memory?

It was actually a conversation with my future undergraduate thesis supervisor, Dr. Ian Dworkin at McMaster University. I was interviewing to join his lab as a summer research student and that was when I learned that changing the diet of flies can reduce how different male and female wing shape and size are. The idea that changing the diet could have such drastic effects on metabolism to the point that organ shape and size are altered is what first drew me into metabolic research.

Could you share your journey into studying metabolism and what inspired you to specialize in metabolic studies using Drosophila melanogaster?

My research journey in metabolism began in flies, and it was truly just luck. I was in a joint-major undergraduate program and part of the requirement was an undergraduate thesis project. I had always planned on going into medical school, so I was late to the game looking for a lab. But a new professor had just joined McMaster’s biology department (Ian), and he took a chance on me. I worked with Ian on understanding how the ratio of macronutrients, or nutritional geometry, affected how different male and female shape and size are using Drosophila wings as a model system. This summer research projected turned into an undergraduate thesis and is what made me fall in love with research. I ended up forgoing applying to medical schools and instead applied for graduate research programs.
From my time with Ian, I knew I wanted to do research in sex differences, continue using Drosophila as my model, and transition to a more biomedical research question. At the time, very few labs focused on investigating sex differences but there was a new lab at the University of British Columbia (UBC) that studied sex differences in metabolism and physiology in Drosophila. This was Dr. Elizabeth Rideout’s lab, and it was the perfect fit for what I wanted to do and is ultimately where I completed my PhD.

How has your transition from working in Drosophila to working in the mammalian system been?

After my PhD, my career goal was to open my own lab that used multiple model systems to bridge the gap between basic science and clinical research. This motivation was why I transitioned to a mammalian lab for my postdoc. The transition for me was fairly smooth as I had ~1yr experience with the Kieffer and Clee labs at UBC using mice. The main differences between using flies and mice for me was how you plan experiments. In flies, you can decide to do an experiment and have the flies ready to go in 1-2 weeks and you can simply do one experiment per cohort. However, with the mice, I would need to have experiments planned over a month in advance (quarantine, breeding, weaning etc) and because it took so much time to have the correct mice for an experiment, you had to maximize what experiments you would perform on each cohort. However, after joining a mouse lab, I quickly realized that I much preferred working with flies to mice. It turns out, I am a geneticist at heart and many of the genetic tools I was used to having in my arsenal in a fly lab did not exist in the mouse world yet. Additionally, while vertebrate model systems are incredibly important for basic research, there is an emotional toll associated with solely using mammalian models. My time in a mammalian lab also helped me realize that I was more interested in understanding the basic science underlying the regulation of metabolism rather than the discovery of new therapeutics to treat metabolic disease. This together with the development of an anaphylactic allergy to mice is what solidified my return to a Drosophila model system.

Tell us how you got interested in the field of nutritional and metabolic aspects of sex differences? How do you think the fields of studying sex differences and metabolism overlap – tell us about your interests in these areas? How have both the sexes evolved to respond to nutrition and metabolic stresses?

One of my motivators for wanting to study metabolism is that my family has a history of type 2 diabetes and obesity – I recently found out that I have a genetic variant that predisposes me to obesity. While starting in the sex differences world was by luck, I decided to stay in this field because I realized just how widespread yet understudied sex differences are (almost every phenotype has a sex difference). Historically, females were omitted from studies because they didn’t show the same phenotypes as males and there was this belief that sex hormones just complicated the data. We can learn so much new biology if we were to include both sexes since males and females form naturally dichotomous groups.
In the case of metabolism, sex differences can be found everywhere from the risk and prevalence of metabolic disease, the response to therapeutics, basal metabolic phenotypes (ie. fat accumulation, blood glucose levels), and the regulation of major metabolic signaling pathways such as insulin and GLP1 (Glucagon-Like Peptide-1). In the metabolism field, is it widely accepted that males and females are phenotypically very different but many studies still only investigate males because females tend to have much weaker responses to metabolic challenges such as high fat diet. To me, this is actually an extremely exciting phenotype. Why are females more protected from developing metabolic dysfunction in response to metabolic challenges? If we could figure out the mechanisms that allow females to be protected, these may be promising avenues for new therapeutics to reverse or alleviate metabolic disease.

Why do you find the basic science aspects exciting ?

I find basic science so exciting because it is the foundation of discovery. We first need to understand normal regulatory processes to understand how these processes become dysfunctional and lead to disease. By investigating how metabolism is regulated in healthy individuals and how these processes can go wrong form the foundation for the development of novel therapeutics to treat metabolic disease. Without basic science, the development of new therapeutics would be significantly hampered.

Why do you think understanding both males and female systems from a metabolic perspective is important? How is it relevant in today’s human health dynamic? Your work is focused on uncovering mechanisms explaining how sex differences in fat metabolism arise, identifying novel functions for metabolic genes and pathways that contribute to how males and females store and break down fat differently. Could you elaborate on the key findings and their implications for the field?

For many years, the metabolism field has known that males and females store and distribute fat differently, and that many metabolic diseases associated with abnormal fat storage hare a male-biased risk and prevalence. While there is a beautiful body of work investigating how sex determination factors (ie. sex chromosomes and sex hormones) establish these sex differences, we lack an understanding of the metabolic genes and metabolic pathways that act downstream of sex determination factors to contribute to the regulation of sex differences in fat metabolism.
My major findings during my PhD were 1) majority of lipid metabolism genes are sex-biasedly regulated, 2) the triglyceride lipase brummer (mammalian ATGL) acts in the somatic cells of the gonad and the neurons to regulate sex differences in fat storage and fat breakdown, 3) lipid droplets are normally present in the neurons (not just diseased states) and may be sex-biasedly regulated by brummer, and 4) the sex determination factor Transformer establishes sex differences in fat metabolism in flies via the sex-biased regulation of the adipokinetic hormone (Akh) signaling pathway. These findings represent novel functions of metabolic effectors and open the doors for interesting questions such as how lipid droplet dynamics in neurons are regulated and how does this impact whole-body fat metabolism, how sex determination factors regulate downstream metabolic effectors like brummer (bmm) and Akh. Also, ATGL inhibition is being investigated in mammals and humans as a potential therapeutic but my data suggests that inhibiting bmm/ATGL function will have greater effects in males than females, thus indicating that ATGL inhibition studies need to be performed in both sexes.

Your work intersects sex differences, metabolism and aging. How do you integrate these disciplines in your research, and what unique insights have emerged from this approach?

I tend to think of sex differences as a tool to understand metabolism. For example, my broad question is how does our brain respond to a high fat diet? Are there certain regions/neuronal populations that become more or less active? How are these high fat diet-induced changes different between males and females? In this way, studying sex differences sheds light on understanding the metabolic phenotype.

You work on sex specific hormonal regulation of lipid metabolism. How difficult were those experiments? Did you have to deal with midnight timepoints or require an army of undergrads/ long hours etc.?

I think the difficulty of any experiment or technique really varies from person to person. For example, molecular techniques such as colorimetric assays and qPCRs came easily to me but I always found imaging more challenging. Having more hands on deck was always a huge bonus because it meant larger or more experiments could be done. For example, if it was just me, I could maybe screen ~5 RNAi lines simultaneously. But if I had 2-3 trainees helping me, that could easily go up to 15-20 RNAi lines. Training and mentoring the next generation of scientists has always been very important to me and I’m really grateful that I had the opportunity to work with so many amazing budding scientists – many of which are recognized as authors on my publications.
As for late night timepoints – this only happened for specific experiments, namely whether circadian rhythm affected the sex difference in fat storage. For this set of experiments, I had a timepoint every 4 hours for a 24 hour period. My philosophy is that I would never have my trainees do something that I wouldn’t do myself so for these experiments, I collected all the samples. While napping on a desk wasn’t the most comfortable, I didn’t mind because I knew this data was important and it wasn’t a regularly occurring experience. I also had the added benefit of Liz (my PhD supervisor) buying me a huge bag of mini eggs to help me make it through the night haha

Building upon your findings in sex-specific fat metabolism and hormonal regulation, what are your upcoming plans? Are there particular metabolic pathways or hormonal regulators you aim to investigate further?

My plans going forward are actually to take a broader look at metabolic function. I mentioned earlier that one well-known sex difference in mammalian metabolism research is that females do not develop metabolic dysfunction to the same degree as males in response to metabolic challenges such as high fat diet. For example, in response to HFD, male mice will develop glucose intolerance and gain more body weight/fat mass than females, and male mice will also have worse cognitive defects after chronic high fat diet than female mice. This together with my previous work suggests that the brain plays a major role in regulating the sex-biased response to HFD. Thus, one major question of my postdoctoral work is what are the brain-wide effects of HFD on neuronal metabolic function? My goal is to use live, volumetric 2-photon imaging in conjunction with genetically-encoded metabolite sensors to investigate how HFD alters neuronal metabolic flux and function in male and female brains.

How are you planning to integrate insect and mammalian models to bridge basic science and therapeutic research?

My current plan for the future is to establish a lab that integrates neurobiology and molecular biology to study how the brain responds to external metabolic stressors (such as chronic diet perturbations or fasting) to regulate whole-body energy homeostasis. My primary model system will likely be Drosophila and any findings that are particularly exciting, I will also investigate in mammalian models, thus allowing me to bridge the gap between invertebrate and vertebrate systems.

What changes have you seen in the research community in regard to studying sex differences ? How do you think scientific paradigms around studying both sexes will evolve in the coming decades? Are we moving toward a more nuanced understanding, or do you see potential pitfalls?

When I started my PhD, I felt that the community acknowledged that sex differences exist but did not think they were important enough to dedicate an entire research project to. In the last decade, I have definitely seen this mentality shift to more appreciation for studies that uncover the mechanisms by which sex differences are established and controlled. We’ve also seen changes in regulations where studies need to justify why they only study one sex and more acknowledgement that what we learn from studying males may not necessarily apply to females. Studies are now also more transparent regarding which sexes are used for specific experiments. This shift towards more studies including both sexes or detailing which sex is used can only be a good thing as it provides us with more data and thus a better understanding of the normal regulatory processes of metabolism. However, even sex is a spectrum with many variations in sex chromosomes. As the field of sex differences evolve, I believe it will become increasingly nuanced until the whole spectrum of sex can be studied to the best of our ability.

How you see the future of metabolism evolve with the new upcoming tools – what techniques have you used and which tools are you most excited about ?

One roadblock that has hampered the discover of new signaling pathways that control metabolism is the identification of ligand-receptor pairs. With the advent of AI-assisted protein structure prediction (eg. AlphaFold, AlphaLigand), the ability to predict receptors for a known ligand or vice versa significantly speeds up our ability to identify metabolic molecular mechanisms. Recent advances have even been able to use AI to predict new drug therapies for example. I think AI will be a really strong tool in a basic scientist’s arsenal.

What role does curiosity play in your life, both within and outside of science? 

Curiosity is a huge part of being a scientist – the desire to know more can really motivate your work. There’s this misconception that scientists know all there is to know about a subject, but if you maintain a child-like sense of wonder or curiosity, you’ll see that there is so much left to learn. When I spend time with my nieces and nephews, my favorite part is hearing their questions because really, every question can lead to a research project. I recently told my niece that our hair and our nails are made of the same thing. She asked me why and I didn’t know. But that could be a budding scientist’s first foray into research.

Were there any pivotal moments that shaped your career path? What advice would you offer to students and early-career scientists interested in exploring the intersections of metabolism and inter-organ communication?

My pivotal moment was joining the Dworkin lab for my undergraduate thesis project – if I hadn’t, I very likely wouldn’t have fallen in love with research and would have gone to medical school.
For anyone interested in research, I would suggest that you think broadly and approach your research question from many angles. While my main focus is on energy metabolism, you can study this from many different points of view such as a neuroscientist or a mathematician.

How do you maintain a balance between your rigorous research activities and personal life? Are there hobbies or practices you find particularly rejuvenating?

I learned the hard way that if you don’t make time for things outside of research, you will burn out. My life outside the lab is equally as important as my time in the lab so I put more effort into planning my work week/month and experiments to maximize the likelihood that I won’t need to be in lab on the weekends or late into the night. Sometimes, that’s just impossible and I work the occasional weekend/late night. Outside the lab, I’m a huge book lover and spend a lot of time reading. I also love to cook and bake. I’ve also been an avid yogi since my undergraduate days so I try to maintain this hobby by going to yoga practice first thing in the morning – I find that waking up early is more reliable than leaving lab at the same time every day.

If you hadn’t embarked on a career in biological research, what other profession might you have pursued, and why?

I’d love to open a cozy bookstore/café hybrid! Somewhere people could get lost among the shelves with a mug of tea. Or maybe that’s just what I want to do haha !

Anything you’d want to highlight ?

I was just selected as one of 2025’s Leading Edge fellows. This is a group of women and non-binary early career scientists that support one another in obtaining R1 faculty positions and tenureship. I’m really proud to be a part of this community to elevate women and non-binary individuals in science.

Last week we learnt about how nutrient dependent signaling shapes cell fate decisions and developmental plasticity in aquatic organisms like sea anemones and planarians. Check out – Of Tor and Tide (Eudald Pascual-Carreras)

Check out the article All the world’s a metabolic dance, and how early career scientists are leading the way !!

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[Behind the paper story of “Synovial joints were present in the common ancestor of jawed fish but lacking in jawless fish”.]

Synovial joints are marvels of biological evolution where two bony segments with curved articular geometries move relative to each other to produce motion and function [1]. In contrast, mechanical joints such as those present in door hinges, machines, and locomotives, also articulate but with simpler geometries, more limited directions of motion, a constant center of rotation, and no natural lubrication. How synovial joints develop fascinated me, especially the role of muscle contraction in joint morphogenesis. Multiple studies over several decades have shown that if the muscles of tetrapod embryos such as mice and chicks are paralyzed, many of their synovial joints remain fused and do not cavitate [2, 3]. I wanted to study the role of embryonic muscle contraction in shaping the articular surface geometries, as learning this relationship may harbor clues on the structure-function relationship of these joints and help design better prosthetics.

To understand the process of joint morphogenesis, I started my postdoctoral research in Neil Shubin’s lab and shifted gears from working in applied mathematics and biomechanics during my PhD to evolutionary developmental biology. Using dissection studies, I identified skates and sharks as the potential model organisms for studying synovial joint development, as they exhibited a large range of motion at the pelvic and jaw joints, and were comprised of striking articular geometries. However, I quickly learned that we did not know whether elasmobranchs have synovial joints at all. Upon deeper investigations, I learned that the situation was even more obscure; we did not know when synovial joints originated in the vertebrate phylogenetic tree! Where did our movable joints come from? I got intrigued by this question and chose to investigate the early evolution of synovial joints before delving into the processes of articular geometry morphogenesis.

Apart from a couple of histological studies from the 1950s in elasmobranchs and chimeras that suggested the presence of cavitated joints, no deeper molecular and developmental investigations had conclusively shown the existence of synovial joints in these groups [4, 5]. To find the origin of synovial joints, I rolled up my sleeves and delved into learning the tools, techniques, scientific thinking, and methods of molecular and evolutionary developmental biology. A recent study out of Gage Crump’s laboratory at the University of Southern California showed how teleosts like zebrafish have synovial-like morphology in their jaw and pectoral fin joints [6]. I identified the two vertebrate clades that phylogenetically precede teleosts with extant representatives, cyclostomes and elasmobranchs, for whom the joint morphology was not clearly understood (Figure 1). I collected adult and juvenile specimens of lamprey and hagfish belonging to the jawless cyclostomes, and little skates and bamboo sharks belonging to jawed elasmobranchs, and performed micro-CT scanning and histological studies to show that little skates and bamboo sharks had cavitated joints. However, we did not find any evidence of cavitated joints in cyclostomes like lamprey and hagfish.

In the absence of cavitated joints, it is infeasible for synovial joints to exist because they need articulating surfaces and function by relative sliding. Therefore, we concluded that cyclostomes do not have synovial joints and focused solely on testing whether the cavitated joints of little skates, belonging to chondrichthyans, a constituent group within elasmobranchs, are synovial-like. Chondrichthyans have a cartilaginous skeleton, and therefore, the conventional definition of synovial joints, described as bony elements covered by a layer of articular cartilage, does not apply. However, if little skates have synovial joints, we expect their articular cartilage and subarticular regions to be morphologically and developmentally similar to tetrapods. To test this, I investigated the collagen proteins that composed the articular and subarticular cartilage in the little skate jaw and pelvis joints. Similar to tetrapods, the subarticular cartilage in the little skates was rich in collagen-II, and the developing articular cartilage in collagen-I (Figure 2).

To test whether the joint cavity in little skates is lubricated, I tested whether any lubricating proteins are present in their articular cartilage (Figure 2). I performed in situ hybridization to locate the expression of lubricin, a key lubricating protein secreted by the articular cartilage and present in synovial fluid, as also shown in the articular cartilage of zebrafish [6]. As a newcomer lacking experience in molecular biology techniques, I did not understand how difficult in situ hybridization experiments can be. After multiple failed experiments for locating the expression of lubricin in little skates, I found a new respect for the experimental endeavors and gave up on looking for lubricin (if somebody is successful, please let me know!). Instead, using immunostaining, I showed the presence of other proteins such as aggrecan and hyaluronic acid receptors in the articular cartilage, also a part of the lubrication assembly [7, 8]. Furthermore, I showed that similar developmental pathways relying on Wnt and BMP signaling underlie joint development in little skate and tetrapods. Finally, using muscle paralysis studies, we also showed that mechanical signals from muscle contraction are necessary for joint cavitation in little skates, similar to tetrapods. Together, our results hypothesize that synovial joints evolved in the common ancestor of extant jawed vertebrates or gnathostomes.

The Shubin lab ecosystem is comprised of developmental biologists, mechanobiologists, and paleontologists. Thus, I have had the opportunity to attend lab meetings that discuss a broad range of approaches and techniques used to solve evolutionary problems. In such meetings, I learned how the extant vertebrate phylogenetic tree only represented a sliver of the actual diversity of vertebrates. The early experimentation in their body plans and morphology was better understood by creating a complete tree with intermediary fossils (Figure 3). I wondered whether we knew about the earliest occurrence of cavitated joints that are similar to the present-day synovial joints in the fossil record, and the answer was no. From the rich phylogeny of early fossil vertebrates, I identified jawless osteostracans and jawed antiarchs as potential clades where synovial joints could have originated. With the help of lab member and friend Yara Haridy, I performed paleohistology on Escuminaspis laticeps, a member of osteostracans, to observe the joint between the shoulder shield and the fin, and analyzed the micro-CT scans of antiarch placoderms, Bothriolepis canadensis and Asterolepis ornata. Our analysis helped infer that cavitated joints existed in placoderms but not osteostracans. Therefore, we minimally placed the presence of first synovial-like cavitated joints in antiarchs, suggesting that synovial joints originated in the common ancestor of all gnathostomes.

With the completion of this study, I have emerged with more understanding of the early evolution and development of synovial joints than when I started, but even more questions. For example, synovial joints exist in two kinds of skeletons, endoskeletal and dermal, relying on different development processes and gene regulation [1]. The dermal skeleton evolved before the endoskeleton, and our inference of synovial joints in placoderms suggests that they first evolved in the dermal skeleton. We also show that the elasmobranch endoskeleton harbors synovial joints. Thus, the evolution of disparate development and regulation to form functionally and morphologically similar synovial joints in the two kinds of skeleton remains enigmatic. My walks in the lands of evolutionary developmental biology have introduced me to a treasure trove of scientific problems that are important to study to understand the evolution of diverse forms and functions. Going forward, I am excited about further understanding the processes of synovial joint morphogenesis and function by combining my training in mechanics, paleontology, and developmental biology with computational biology.

References

[1] Pallavi Juneja, Akul Munjal, and John B Hubbard. Anatomy, joints. 2018.

[2] Joy Kahn, Yulia Shwartz, Einat Blitz, Sharon Krief, Amnon Sharir, Dario A Breitel, Revital Rattenbach, Frederic Relaix, Pascal Maire, Ryan B Rountree, et al. Muscle contraction is necessary to maintain joint progenitor cell fate. Developmental cell, 16(5):734–743, 2009.

[3] PDF Murray and Daniel B Drachman. The role of movement in the development of joints and related structures: the head and neck in the chick embryo. Development, 22(3):349–371, 1969.

[4] DV Davies. The synovial joints of the skate (raia). Journal of anatomy, 82(Pt 1-2):9, 1948.

[5] R Wheeler Haines. Eudiarthrodial joints in fishes. Journal of Anatomy, 77(Pt 1):12, 1942.

[6] Amjad Askary, Joanna Smeeton, Sandeep Paul, Simone Schindler, Ingo Braasch, Nicholas A Ellis, John Postlethwait, Craig T Miller, and J Gage Crump. Ancient origin of lubricated joints in bony vertebrates. Elife, 5:e16415, 2016.

[7] Jasmine Seror, Yulia Merkher, Nir Kampf, Lisa Collinson, Anthony J Day, Alice Maroudas, and Jacob Klein. Articular cartilage proteoglycans as boundary lubricants: structure and frictional interaction of surface-attached hyaluronan and hyaluronan–aggrecan complexes. Biomacromolecules, 12(10):3432–3443, 2011.

[8] TS Momberger, JR Levick, and RM Mason. Hyaluronan secretion by synoviocytes is mechanosensitive. Matrix Biology, 24(8):510–519, 2005.

(3 votes)
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BSDB Report co-written by Simran Singh and Renato Duarte Dos Santos

We are extremely grateful to the BSDB for giving us the opportunity to attend the Biologists @ 100 conference in Liverpool. As PhD students investigating spinal cord injury and regeneration, this experience was invaluable. It allowed us to connect with scientists, gain insights into diverse fields and explore potential collaborations.

Simran Singh

The meeting started off with an exciting early career research session, offering a unique chance to interact with individuals who have pursued various scientific career paths. A highlight for me was the keynote talk by Dr. Richard Server, co-founder of bioRxiv and medRxiv. He shared his career trajectory, discussed the impact of bioRxiv on publishing – especially during the Covid-19 pandemic –and highlighted the numerous transferable skills gained from an academic career.

The following three days were filled with inspiring and thought-provoking scientific talks. One of the first talks was by Professor Muzlifah Haniffa, recipient of the Cheryll Tickle Medal. She described herself as “born into immunology, married into developmental biology, and became best friends with single-cell omics”. Her research focuses on decoding the human immune system, particularly the spatial and temporal composition of immune cells and their roles beyond immunology, such as in development. Additionally, her work on the Human Developmental Cell Atlas, integrating developmental disorders, has had a profound translational impact. Throughout her talk, she emphasised the importance of interdisciplinary approaches and collaboration in science. She is also a strong advocate for women in STEM and leadership. I particularly liked her powerful statement “Women should continue to thrive in science not despite but because of the system”.

Another talk I enjoyed was by Professor Helen Skaer, winner of the BSDB Waddington Award for her outstanding research, contributions to the developmental biology community and excellent mentorship. Her research explores how cells work together to make an organ of the right shape, size and in the right place, with a focus on renal tubules in fruit flies, which are highly consistent. She eloquently described her research journey from studying Mercierella Enigmatica (reef building tubeworms) to fruit flies and shared some of her “most exciting moments” in the lab. One such moment was the identification of a ‘tip cell’, the master regulator that when ablated would arrest cell division of the renal tubules. My favourite part was due to the lack of a laser ablation machine, Professor Helen Skaer had to come up with a creative solution to manually “suck up” the tip cell. It reminded me the importance of being creative in research and not being afraid to think outside the box.

Overall, I had a great time at the Biologists@100 conference. It was a fantastic opportunity to hear talks from scientists across the world. I am now ready to go back into the lab feeling more inspired than ever!

Renato Duarte Dos Santos

Spreading science for 100 years, The Company of Biologists and BSDB have delivered an amazing event full of opportunities to learn more about the current work in developmental biology, but also in environmental awareness and career pathing in biology. This year, the developmental biology showcase at the conference had a clear focus on the role of signal patterning and mechanical signaling, which has been shown to affect multiple processes that we tend to view as solely based on biochemical reactions.

I had a special interest in the work done by Dr. Muzlifah Haniffa, awarded the BSDB Tickle Medal for her involvement in the Human Development  Cell Atlas, a project aiming to incorporate single-omics from all human cells that intervene in human development. I believe this tool will become intemporal for the world of science, with applications for all the multitude of biomedical-related fields.

Another work that caught my eye was the development of a new barcoding method and bioinformatic processing capable of improving the output of single-cell expression analysis, increasing the sampling and reducing substantially the price in comparison with the current market offer (Maizels et al., 2024). This amazing work has been done by Dr. Rory Maizels while as a PhD student. His brilliance and achievements have led him to be awarded the well-deserved BSDB PhD student Beddington Medal. Another approach that I found very interesting was the use of the cell shape to determine the cell type and cell fate, like a pseudo-time analysis (Pönisch et al., 2024 preprint). This innovative work was made by Ewa Paluch from the University of Cambridge.

Besides development talks, there were also some morning plenary talks about climate change and biodiversity loss to help spread awareness about this urgent global matter that hasn’t been handled so far as it should.

I also found the early-career researcher career session quite insightful. It helped me and most likely many to gain a realistic view of the current scientific paradigm and the many options we biologists possess in terms of profession. The chance to have a one-to-one talk with a professional of each career path was for sure one of the most useful experiences. I also have to mention the gala dinner, which was of the highest luxury in a mouth-dropping location, the St George’s Hall. Overall, the conference was amazing, full of great talks, opportunities to network with high-tier researchers, and to enjoy the scientific community at its best.

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One of my favourite uses of social media is sharing (and discovering) new preprints that seem relevant for my field. Rewardingly, posting preprints is usually well-received by followers. Since there used to be a button on the bioRxiv website for posting preprints on twitter/X, this was a relatively simple thing to do. However, twitter/X is abandoned and the majority of folks that I follow are now on Bluesky. So, now I’m posting preprints (among other sciency content) on BlueSky. Unfortunately, at the time of writing this piece, there are no buttons on the bioRxiv page that facilitate this process.

The information that I collect for posting the preprint are the title, an author and the link to the preprint, so that involves quite some copy-pasting between different browser windows. To simplify this process, I looked into web extensions (footnote 1). The web extensions that I needed was not there, so I decided to explore how easy it is to make one. It turns out that web extensions are written in Javascript and I have zero experience with this language. So, I turned to AI for help.

First, I tried ChatGPT, which wasn’t very successful. Then, I turned to Claude.ai and I got a working prototype after my first prompt. After a second prompt I already had something quite decent. Then, I decided to polish the web extension, e.g. add an icon, add only the name of the last author to the post and extend the functionality to medRxiv. This process involved several iterations of prompts and tests. The main issue is that new functionality has to be added without breaking the existing functions. So there were several rounds where the code stopped working, and I had to feed the error to Claude.ai and ask for repair. I also asked several times to ‘simplify the code’, to keep the code concise. In the end (17 prompts in total), I got a nicely working extension that shows a blue icon when a preprint can be shared and when the icon is clicked a post for BlueSky is prepared. This is exactly what I needed! The code for the extension (for the Firefox web browser) and an instruction to install it are available here: https://github.com/JoachimGoedhart/Rxiv2BlueSky

Besides the tangible result, I also gained some insight of how Large-Language Models can augment the development of software. Without any knowledge of web extensions, nor the necessary language needed to create one, I was able to generate a nicely working add-on, by simply defining what I wanted to achieve. Later on, I learned that this process is known as ‘vibe-coding’, a term introduced by Andrej Karpathy. The exciting point is that vibe coding enables non-coders to generate working code. For me, vibe coding a web extension was an amazing experience and it felt like I gained some kind of superpower.

Footnotes

Footnote 1: I wasn’t familiar with web extensions at all and it turned out that there is an ecosystem of different extension for different browsers and in some cases developers have to pay to publish their extension. Since I’m commonly using Firefox (in some cases Safari), and since publishing extensions (or add-ons) for Firefox is free, I decided to go for Firefox as the browser.

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In this SciArt profile, we meet Margot Smit, a plant developmental biologist whose lab is in the ZMBP, University of Tübingen. Margot enjoys linocut printmaking of designs inspired by Arabidopsis images from the lab and scenes from nature.

Can you tell us about your background and what you work on now?

I’m a Plant Developmental Biologist working on the temporal regulation of cell identity. In my lab we are using the Arabidopsis embryo and its stomatal lineage to study examples of temporal cell identity control. I studied Biotechnology in Wageningen (Netherlands) and quickly became interested plant developmental biology and during my MSc and PhD I studied the regulation of vascular identity specification during Arabidopsis embryogenesis. After years studying vascular development, I moved to Stanford University to study stomata. Right now, in Tübingen, we use embryonic stomatal development to study the temporal regulation of developmental decisions.

Were you always going to be a scientist?

No, I didn’t really realize that scientist was a real job until I was doing my BSc thesis. I thought it was like becoming an astronaut; some people get to do it but it’s very out of reach for me. During my BSc thesis project, I fell in love with the scientific method of identifying and trying to answer basic questions in biology. I’ve always loved puzzles and all of it felt and still feels like a lovely, complex puzzle. I didn’t know whether I would be able to continue in academia, but I’ve just been taking it one step at a time and enjoying the journey.

And what about art – have you always enjoyed it?

I’ve always enjoyed art and got a lot of opportunities to play around with it growing up but was never super confident. Several of my family members are very artistic and have attended and/or taught at art schools which got me exposed at a young age. However, I am not incredibly talented and do not have the patience or practice with drawing or painting: I make a lot of mistakes and easily give up on it. Instead, during my PhD I discovered a love for using Illustrator to create fun compositions and designs.

What or who are your most important artistic influences?

My mother, grandma and aunt were my first artistic influences growing up, there were always plenty of art supplies and examples around. While traveling in Eureka few years ago, I saw prints from Lynn M Jones and got inspired to give it a try. I then took Katie Gilmartin’s awesome printmaking course in San Francisco and she’s been a great inspiration. In recent years I’ve also been really inspired by online communities sharing their printmaking. For me, most prints are based on images from the lab or from nature.

How do you make your art?

Each print starts with a series of images or ideas. The challenge for me is to figure out how to work with the restrictions that are part of my linocut printmaking process. I usually only carve one or two blocks per print and a design needs to be high contrast, relatively simplistic, and mostly two-tone with limited shading options. First, I try lots of different designs using Illustrator and my drawing tablet. Once I am satisfied with the design, I transfer it to the linoleum and start carving. When I think I am done I will do some test prints and maybe adjust the carving before moving to the real printing. To print I use oil-based inks that I mix to the desired color and apply using a roller. Then I place a sheet of damp paper on top and start to transfer the ink: for small blocks I can use my press, for larger blocks I have to hand print using a baren. Depending on the depth of the lines I will print each block five to twenty times.

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

For me they are very connected. A lot of my prints are based on images from the lab or based on scientific interests. That’s one of the cool aspects of working with plants, patterns and embryos.

What are you thinking of working on next?

I’ve started a new project with a bunch of scientific model organisms. But things have been busy at work recently and while I am done with the design, I haven’t progressed far into the carving yet. I think it’ll be a challenge to print but that’s part of the fun.

How can people find more about you and your artwork?

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Reproduction is a metabolically costly process. Therefore, the proper regulation of physiological changes in the mother during pregnancy and lactation is crucial for fetal development and neonatal growth. In many mammals, including humans, pregnancy induces systemic changes in hormonal, metabolic, and immune functions.¹ Reproductive-associated changes are also known to occur at the organ level, in particular, an increase in intestinal size during pregnancy and lactation has been observed in several mammals such as mice, rats, sheep, and pigs.^2,3 However, despite the first report of this phenomenon, documented in 1939,⁴ the molecular mechanisms underlying maternal intestinal remodelling during reproduction, as well as their physiological significance, have only recently begun to be investigated.⁵

Studies using fruit flies have shed light on the molecular mechanisms regulating reproductive plasticity and sex differences in adult digestive tract. ^6–13 Instead of studying the fly, we decided to focus on the maternal intestinal growth in mice.

Characterising maternal gut growth in epithelium

We first examined the organ size of the small intestine during reproduction and observed that the maternal small intestine is significantly longer and heavier than that of non-pregnant female mice, consistent with previous studies.^14,15 Notably, the small intestine remains elongated even one month after weaning, suggesting that gut elongation is an irreversible (or only partially reversible) process.

Next, we investigated the mucosal morphology of the small intestine, which consists of absorptive villi (finger-like projections into the lumen) and crypts (which house progenitor cells). We observed that both villi and crypts increased in size during pregnancy and lactation (Figure 1). Since the size of the crypt-villus structure can be determined by the number and size of epithelial cells—or both—we focused on epithelial proliferation. The intestinal epithelium has one of the fastest turnover rates among all tissues, typically renewing every 3–5 days.

We found that this turnover rate was accelerated during reproduction, with lactating mice exhibiting the highest turnover rate—renewing in just 1.3 days. In contrast to the irreversible elongation of the gut tube, the growth of the gut epithelium is reversible: both the crypt-villus structure and epithelial turnover returned to pre-pregnancy levels within one week after weaning. These results suggest that gut tube elongation and epithelial growth are regulated by different mechanisms.

Remodelling of epithelial cell types in the gut

We have two hypotheses of how the crypt-villus structure enlarges:

1. Do epithelial cells increase proportionally across different cell types at a similar rate?
2. Or do epithelial cells increase preferentially in specific cell types?

To address this question, we first analysed our single-cell RNA sequencing data from FACS-sorted intestinal epithelial cells, where we did not observe significant differences in cell composition between reproductive and non-reproductive mice. However, since it was unclear whether this lack of difference was due to technical—such as the dissociation of epithelial cells and the FACS-sorting process—or biological reasons, we decided to perform a spatial imaging analysis using the Xenium in situ platform. We profiled subtypes of intestinal epithelial cells—including absorptive enterocytes, secretory cells, and progenitor cells—to compare cell composition between intestines from reproductive and non-reproductive mice.

We actually found that lactating mice had significantly more progenitor cells, specifically isthmus progenitors in the upper crypts, along with their neighbouring enterocytes located at the base of the villi. This indicates that epithelial cell expansion during reproduction occurs preferentially in specific cell types.

While the reason for this preferential increase is still unclear, we speculate that the expansion of the progenitor population supports the accelerated epithelial turnover observed during lactation.

What is the molecular mechanism behind this?

To uncover potential drivers of maternal gut growth, we focused on a transporter gene called SGLT3a, whose expression was upregulated in our transcriptomics datasets—including whole small intestine tissue, FACS-sorted intestinal epithelial cells, and spatial imaging analysis—during reproduction. SGLT stands for sodium-glucose cotransporter, but previous studies have shown that, unlike SGLT1 (which transports glucose from the lumen into epithelial cells), SGLT3a does not function as a sugar transporter, at least at physiological pH.¹⁶

To investigate its function in vivo, we performed a series of phenotypic analyses using SGLT3a knockout mice. The knockout mice appeared physiologically normal under standard conditions; their food intake, body weight, and glucose tolerance were comparable to those of control littermates.

Importantly, however, maternal gut epithelial growth—both in terms of crypt-villus morphology and epithelial turnover—was significantly reduced in SGLT3a knockout mice during lactation. This effect appears to be specific to the reproductive state, as we did not observe similar phenotypes in non-pregnant female knockout mice. We also observed that progenitor proliferation was dampened in intestinal organoids—mini-guts grown in vitro—derived from SGLT3a knockout mice, suggesting a gut-specific role of SGLT3a in regulating maternal gut epithelial growth.

What are the downstream signals?

How does SGLT3a control villus growth during reproduction? We found that the population of progenitor cells expressing Fgfbp1—a known marker for isthmus progenitors^17,18—was reduced in SGLT3a knockout mice. Since SGLT3a is not expressed in progenitor cells themselves, we hypothesise that SGLT3a expressed in enterocytes regulates progenitor proliferation extrinsically through Fgfbp1 expression.

Our electrophysiological experiments demonstrated that SGLT3a responds to protons and sodium, but not to sugars. Sodium is an especially intriguing candidate, as we observed that dietary sodium can mimic the effects of reproduction on the gut epithelium. Therefore, it would be interesting to further explore whether dietary sodium is essential for maternal organ remodelling, including that of the small intestine.

What are the upstream signals?

Could the upregulation of SGLT3a be driven by increased food intake during reproduction? This seems unlikely, as SGLT3a expression is already elevated by early pregnancy (gestational day 7), which precedes the marked increase in maternal food intake observed in mid-pregnancy. This suggests that other signals may be responsible for inducing SGLT3a expression in the intestinal epithelium.

One possible group of candidates is reproductive hormones. In our single-cell transcriptomic analysis of intestinal epithelial cells, we observed broad expression of the prolactin receptor, whereas estrogen and progesterone receptors were either undetectable or expressed at very low levels. Supporting this, we found that treating intestinal organoids with prolactin led to upregulation of SGLT3a expression.

These findings suggest that reproductive hormones—particularly prolactin—may play a role in this process by driving pregnancy-specific SGLT3a induction. Further research is needed to investigate how hormonal signals, or signals originating outside the intestinal epithelium,⁵ contribute to SGLT3a induction and maternal gut growth during reproduction.

What is the physiological relevance?

Despite no significant difference in litter size at birth, we observed a lower survival rate among pups born to SGLT3a knockout mothers compared to those born to wild-type mothers. Although we cannot exclude the possibility that this phenotype is influenced by SGLT3a function outside the gut—given that whole-body knockout mice were used—our findings suggest that SGLT3a contributes to reproductive success by sustaining maternal gut growth during pregnancy. It would be intriguing to investigate the long-term effects on both mothers and offspring, as excessive weight gain during pregnancy and after childbirth in humans is known to be associated with an increased risk of chronic diseases in mothers and future obesity in their children.

Access the article­: Ameku T, Laddach A, Beckwith H, Milona A, Rogers LS, Schwayer C, Nye E, Tough IR, Thoumas JL, Gautam UK, Wang YF, Jha S, Castano-Medina A, Amourda C, Vaelli PM, Gevers S, Irvine EE, Meyer L, Andrew I, Choi KL, Patel B, Francis AJ, Studd C, Game L, Young G, Murphy KG, Owen B, Withers DJ, Rodriguez-Colman M, Cox HM, Liberali P, Schwarzer M, Leulier F, Pachnis V, Bellono NW, Miguel-Aliaga I. Growth of the maternal intestine during reproduction. Cell. 2025 Mar 19:S0092-8674(25)00200-4. doi: 10.1016/j.cell.2025.02.015. Epub ahead of print. PMID: 40112802.

References

1. Napso T, Yong HEJ, Lopez-Tello J, Sferruzzi-Perri AN. The Role of Placental Hormones in Mediating Maternal Adaptations to Support Pregnancy and Lactation. Front Physiol. 2018 Aug 17;9:1091. doi: 10.3389/fphys.2018.01091. PMID: 30174608.
2. Hammond KA. Adaptation of the maternal intestine during lactation. J Mammary Gland Biol Neoplasia. 1997 Jul;2(3):243-52. doi: 10.1023/a:1026332304435. PMID: 10882308.
3. Speakman JR. The physiological costs of reproduction in small mammals. Philos Trans R Soc Lond B Biol Sci. 2008 Jan 27;363(1490):375-98. doi: 10.1098/rstb.2007.2145. PMID: 17686735.
4. Poo LJ, Lew W, Addis T. Protein anabolism of organs and tissues during pregnancy and lactation. J. Biol. Chem. 1939 Volume 128, Issue 1, Pages 69-77, ISSN 0021-9258.
5. Onji M, Sigl V, Lendl T, Novatchkova M, Ullate-Agote A, Andersson-Rolf A, Kozieradzki I, Koglgruber R, Pai TP, Lichtscheidl D, Nayak K, Zilbauer M, Carranza García NA, Sievers LK, Falk-Paulsen M, Cronin SJF, Hagelkruys A, Sawa S, Osborne LC, Rosenstiel P, Pasparakis M, Ruland J, Takayanagi H, Clevers H, Koo BK, Penninger JM. RANK drives structured intestinal epithelial expansion during pregnancy. Nature. 2025 Jan;637(8044):156-166. doi: 10.1038/s41586-024-08284-1. Epub 2024 Dec 4. PMID: 39633049.
6. Blackie L, Gaspar P, Mosleh S, Lushchak O, Kong L, Jin Y, Zielinska AP, Cao B, Mineo A, Silva B, Ameku T, Lim SE, Mao Y, Prieto-Godino L, Schoborg T, Varela M, Mahadevan L, Miguel-Aliaga I. The sex of organ geometry. Nature. 2024 Jun;630(8016):392-400. doi: 10.1038/s41586-024-07463-4. Epub 2024 May 29. PMID: 38811741.
7. White MA, Bonfini A, Wolfner MF, Buchon N. Drosophila melanogaster sex peptide regulates mated female midgut morphology and physiology. Proc Natl Acad Sci U S A. 2021 Jan 5;118(1):e2018112118. doi: 10.1073/pnas.2018112118. PMID: 33443193.
8. Hadjieconomou D, King G, Gaspar P, Mineo A, Blackie L, Ameku T, Studd C, de Mendoza A, Diao F, White BH, Brown AEX, Plaçais PY, Préat T, Miguel-Aliaga I. Enteric neurons increase maternal food intake during reproduction. Nature. 2020 Nov;587(7834):455-459. doi: 10.1038/s41586-020-2866-8. Epub 2020 Oct 28. Erratum in: Nature. 2020 Dec;588(7839):E36. doi: 10.1038/s41586-020-3013-2. PMID: 33116314.
9. Zipper L, Jassmann D, Burgmer S, Görlich B, Reiff T. Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ-homolog Eip75B in Drosophila. Elife. 2020 Aug 10;9:e55795. doi: 10.7554/eLife.55795. PMID: 32773037.
10. Ahmed SMH, Maldera JA, Krunic D, Paiva-Silva GO, Pénalva C, Teleman AA, Edgar BA. Fitness trade-offs incurred by ovary-to-gut steroid signalling in Drosophila. Nature. 2020 Aug;584(7821):415-419. doi: 10.1038/s41586-020-2462-y. Epub 2020 Jul 8. PMID: 32641829.
11. Hudry B, de Goeij E, Mineo A, Gaspar P, Hadjieconomou D, Studd C, Mokochinski JB, Kramer HB, Plaçais PY, Preat T, Miguel-Aliaga I. Sex Differences in Intestinal Carbohydrate Metabolism Promote Food Intake and Sperm Maturation. Cell. 2019 Aug 8;178(4):901-918.e16. doi: 10.1016/j.cell.2019.07.029. PMID: 31398343.
12. Hudry B, Khadayate S, Miguel-Aliaga I. The sexual identity of adult intestinal stem cells controls organ size and plasticity. Nature. 2016 Feb 18;530(7590):344-8. doi: 10.1038/nature16953. PMID: 26887495.
13. Reiff T, Jacobson J, Cognigni P, Antonello Z, Ballesta E, Tan KJ, Yew JY, Dominguez M, Miguel-Aliaga I. Endocrine remodelling of the adult intestine sustains reproduction in Drosophila. Elife. 2015 Jul 28;4:e06930. doi: 10.7554/eLife.06930. PMID: 26216039.
14. CAMPBELL RM, FELL BF. GASTRO-INTESTINAL HYPERTROPHY IN THE LACTATING RAT AND ITS RELATION TO FOOD INTAKE. J Physiol. 1964 May;171(1):90-7. doi: 10.1113/jphysiol.1964.sp007363. PMID.
15. Casirola DM, Ferraris RP. Role of the small intestine in postpartum weight retention in mice. Am J Clin Nutr. 2003 Dec;78(6):1178-87. doi: 10.1093/ajcn/78.6.1178. PMID: 14668281.
16. Barcelona S, Menegaz D, Díez-Sampedro A. Mouse SGLT3a generates proton-activated currents but does not transport sugar. Am J Physiol Cell Physiol. 2012 Apr 15;302(8):C1073-82. doi: 10.1152/ajpcell.00436.2011. Epub 2012 Feb 1. PMID: 22301059.
17. Capdevila C, Miller J, Cheng L, Kornberg A, George JJ, Lee H, Botella T, Moon CS, Murray JW, Lam S, Calderon RI, Malagola E, Whelan G, Lin CS, Han A, Wang TC, Sims PA, Yan KS. Time-resolved fate mapping identifies the intestinal upper crypt zone as an origin of Lgr5+ crypt base columnar cells. Cell. 2024 Jun 6;187(12):3039-3055.e14. doi: 10.1016/j.cell.2024.05.001. PMID: 38848677.
18. Malagola E, Vasciaveo A, Ochiai Y, Kim W, Zheng B, Zanella L, Wang ALE, Middelhoff M, Nienhüser H, Deng L, Wu F, Waterbury QT, Belin B, LaBella J, Zamechek LB, Wong MH, Li L, Guha C, Cheng CW, Yan KS, Califano A, Wang TC. Isthmus progenitor cells contribute to homeostatic cellular turnover and support regeneration following intestinal injury. Cell. 2024 Jun 6;187(12):3056-3071.e17. doi: 10.1016/j.cell.2024.05.004. PMID: 38848678.

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A workshop to explore how synthetic biology can help us understand how embryos build themselves

20 – 21 October 2025, Brighton, UK. A Royal Society Theo Murphy meeting organised by Jake Cornwall-Scoones,  Dirk Benzinger, and Sally Lowell.

As systems-level measurement of embryogenesis reaches maturity, developmental biologists are returning to foundational questions of how embryos build themselves. Synthetic biology has demonstrated how bottom-up explanations reveal design principles of biological transitions, and is increasingly looking towards embryos for inspiration, holistic contextualisation, and evolutionary interpretation. This meeting brings together these two disciplines towards a science of generative biology.

Speakers:

Philip Ball : David Brückner : Francesca Ceroni : Jamie Davies : Pulin Li : Mattias Malaguti : Yolanda Schaerli : Ricard Solé : Berna Sozen : Ben Steventon : Jared Toettcher : Vikas Trivedi : Berta Verd : Sara Wickström

Places available for short talks and posters.

https://www.royalsoc.ac.uk/science-events-and-lectures/2025/10/generative-biology

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