To accompany the Biologists @ 100 conference, we are launching the Node–FocalPlane image competition.
Enter your best biological research images for your chance to win £250. All the shortlisted images will be presented in our gallery at Biologists @ 100 at ACC Liverpool, 24-27 March 2025 and on the Node and FocalPlane.
Voting will begin the week before the conference and will continue until Thursday 27 March, when the winner will be announced at the conference and online.
Entries are open to all researchers whether you are attending Biologists @ 100 or not.
Deadline for submissions: 24 February 2025
Registration for Biologists @ 100 is open until 28 February. Join us in Liverpool for the chance to see your image displayed in our gallery! The programme overview is available here and the details of the cell and developmental biology track can be found here.
Competition details:
Email your image to thenode@biologists.com with ‘Biologists @ 100 image competition’ in the subject line.
You can submit up to three biological scientific research images that fall within the scope of The Company of Biologists‘ journals.
In the email, include a description of the image and imaging modality used to acquire the image or software used to reconstruct or analyse it.
We’ll require a high-resolution version if you image is shortlisted. You can submit downsampled images for the initial selection.
There is no theme and no restriction content-wise; it can be a raw, reconstructed, filtered or analysed image of any type of biological sample.
Deadline for image submission is 24 February 2025.
Submitted images should not have already been published elsewhere unless under a CC-BY license and should not have been submitted in another image competition.
One first place prize – £250 and two runners up prizes – £125
Image credit: Antara Chakraborty (No Ratings Yet) Loading...
Luuli N. Tran, Ashwini Shinde, Kristen H. Schuster, Aiman Sabaawy, Emily Dale, Madalynn J. Welch, Trevor J. Isner, Sylvia A. Nunez, Fernando García-Moreno, Charles G. Sagerström, Bruce H. Appel, Santos J. Franco
C. Schwayer, S. Barbiero, D. B. Brückner, C. Baader, N. A. Repina, O. E. Diaz, L. Challet Meylan, V. Kalck, S. Suppinger, Q. Yang, J. Schnabl, U. Kilik, J. G. Camp, B. Stockinger, M. Bühler, M. B. Stadler, E. Hannezo, P. Liberali
Marek J. van Oostrom, Yuting I. Li, Wilke H. M. Meijer, Tomas E. J. C. Noordzij, Charis Fountas, Erika Timmers, Jeroen Korving, Wouter M. Thomas, Benjamin D. Simons, Katharina F. Sonnen
Shariq S. Ansari, Miriam E. Dillard, Mohamed Ghonim, Yan Zhang, Daniel P. Stewart, Robin Canac, Ivan P. Moskowitz, William C. Wright, Christina A. Daly, Shondra M. Pruett-Miller, Jeffrey Steinberg, Yong-Dong Wang, Taosheng Chen, Paul G. Thomas, James P. Bridges, Stacey K. Ogden
Iona G. Thelwall, Carola M. Morell, Dominika Dziedzicka, Lucia Cabriales, Andrew Hodgson, Floris J.M. Roos, Louis Elfari, Ludovic Vallier, Kevin J. Chalut
Eunah Chung, Fariba Nosrati, Mike Adam, Andrew Potter, Mohammed Sayed, Benjamin D. Humphreys, Hee-Woong Lim, Yueh-Chiang Hu, S. Steve Potter, Joo-Seop Park
Rui Yan, Ludwig A. Hoffmann, Panagiotis Oikonomou, Deng Li, ChangHee Lee, Hasreet Gill, Alessandro Mongera, Nandan L. Nerurkar, L. Mahadevan, Clifford J. Tabin
Indhujah Thevarajan, Maria F. Osuna, Sonia Fuentes Lewey, Eustolia Sauceda, Sayra Briseno, Caylah Griffin, Bareun Kim, R. Grant Rowe, Edroaldo Lummertz da Rocha, Jihan K Osborne
Meghana S. Oak, Marco Stock, Matthias Mezes, Tobias Straub, Antony M. Hynes-Allen, Jelle van den Ameele, Ignasi Forne, Andreas Ettinger, Axel Imhof, Antonio Scialdone, Eva Hörmanseder
Anita Adami, Raquel Garza, Patricia Gerdes, Pia A. Johansson, Fereshteh Dorazehi, Symela Koutounidou, Laura Castilla-Vallmanya, Diahann A.M. Atacho, Yogita Sharma, Jenny G. Johansson, Oliver Tam, Agnete Kirkeby, Roger A. Barker, Molly Gale-Hammell, Christopher H. Douse, Johan Jakobsson
Alexander Stanton, Selcan Aydin, Daniel A. Skelly, Dylan Stavish, Kim Leonhard, Seth Taapken, Erik McIntire, Matthew Pankratz, Anne Czechanski, Tenneille Ludwig, Ted Choi, Steven P. Gygi, Ivana Barbaric, Steven C. Munger, Laura G. Reinholdt, Martin F. Pera
Rajini Chandrasegaram, Antony M. Hynes-Allen, Beitong Gao, Abhilesh Dhawanjewar, Michele Frison, Stavroula Petridi, Patrick F. Chinnery, Hansong Ma, Jelle van den Ameele
Valentina Sica, Jacob G Smith, Oleg Deryagin, Eva Andres, Vera Lukesova, Mirijam Egg, Nina Cabezas-Wallscheid, Salvador Aznar Benitah, Antonio L. Serrano, Eusebio Perdiguero, Pura Muñoz-Cánoves
Yuanyuan Qin, Parth Chhetri, Elizabeth Theusch, Grace Lim, Sheila Teker, Yu-Lin Kuang, Shahrbanoo Keshavarz Aziziraftar, Mohammad Hossein Mehraban, Antonio Munoz-Howell, Varun Saxena, Dounia Le Guillou, Aras N. Mattis, Jacquelyn J. Maher, Marisa W. Medina
Sarah Stucchi, Lessly P. Sepulveda-Rincon, Camille Dion, Gaja Matassa, Alessia Valenti, Cristina Cheroni, Alessandro Vitriolo, Filippo Prazzoli, George Young, Marco Tullio Rigoli, Martina Ciprietti, Benedetta Muda, Zoe Heckhausen, Petra Hajkova, Nicolò Caporale, Giuseppe Testa, Harry G. Leitch
F. Soares-da-Silva, G. Nogueira, Marie-Pierre Mailhe, L. Freyer, A. Perkins, S. Hatano, Y. Yoshikai, P. Pereira, A. Bandeira, R. Elsaid, E. Gomez-Perdiguero, A. Cumano
Tae Wan Kim, Jinghua Piao, Vittoria D Bocchi, So Yeon Koo, Se Joon Choi, Fayzan Chaudhry, Donghe Yang, Hyein S Cho, Emiliano Hergenreder, Lucia Ruiz Perera, Subhashini Joshi, Zaki Abou Mrad, Nidia Claros, Shkurte Ademi Donohue, Anika K. Frank, Ryan Walsh, Eugene V. Mosharov, Doron Betel, Viviane Tabar, Lorenz Studer
Andrzej Kubiak, Natalia Bryniarska-Kubiak, Mehmet Eren, Kacper Kowalski, Kinga Gawlińska, Patrycja Kwiecińska, Martine Biarnes-Pelicot, Marie Dessard, Jana El Husseiny, Ti-Thien N-Guyen, Pawel Kożuch, Olga Lis, Marta Targosz-Korecka, Pierre-Henri Puech, Krzysztof Szade
Antonella F.M. Dost, Katarína Balážová, Carla Pou Casellas, Lisanne M. van Rooijen, Wisse Epskamp, Gijs J.F. van Son, Willine J. Wetering, Carmen Lopez-Iglesias, Harry Begthel, Peter J. Peters, Niels Smakman, Johan H. van Es, Hans Clevers
Xi Chen, Krishnan Raghunathan, Bin Bao, Elsy Ngwa, Andrew Kwong, Zhongyang Wu, Stephen Babcock, Clara Baek, George Ye, Anoohya Muppirala, Qianni Peng, Michael Rutlin, Mantu Bhaumik, Daping Yang, Daniel Kotlarz, Unmesh Jadhav, Meenakshi Rao, Eranthie Weerapana, Xu Zhou, Jose Ordovas-Montanes, Scott B. Snapper, Jay R. Thiagarajah
Alejandro Roisman, Leonardo Rivadeneyra, Lindsey Conroy, Melissa M. Lee-Sundlov, Natalia Weich, Simon Glabere, Shikan Zheng, Katelyn E. Rosenbalm, Mark Zogg, George Steinhardt, Anthony J. Veltri, Joseph T. Lau, Tongjun Gu, Hartmut Weiler, Ramon C. Sun, Karin M. Hoffmeister
Connor J. Powell, Hani D. Singer, Ashley R. Juarez, Ryan T. Kim, Duygu Payzin-Dogru, Aaron M. Savage, Noah J. Lopez, Steven J. Blair, Adnan Abouelela, Anita Dittrich, Stuart G. Akeson, Miten Jain, Jessica L. Whited
Maria Jassinskaja, Daniel Bode, Monika Gonka, Theodoros I Roumeliotis, Alexander J Hogg, Juan A Rubio Lara, Ellie Bennett, Joanna Milek, Bart Theeuwes, M S Vijayabaskar, Lilia Cabrera Cosme, James L C Che, Sandy MacDonald, Sophia Ahmed, Benjamin A Hall, Grace Vasey, Helena Kooi, Miriam Belmonte, Mairi S Shepherd, William J Brackenbury, Iwo Kucinski, Satoshi Yamazaki, Andrew N Holding, Alyssa H Cull, Nicola K Wilson, Berthold Göttgens, Jyoti Choudhary, David G Kent
Rohan Kulkarni, Chinmayee Goda, Alexander Rudich, Malith Karunasiri, Amog P Urs, Yaphet Bustos, Ozlen Balcioglu, Wenjun Li, Sadie Chidester, Kyleigh A Rodgers, Elizabeth AR Garfinkle, Ami Patel, Katherine E Miller, Phillip G Popovich, Shannon Elf, Ramiro Garzon, Adrienne M Dorrance
Li’ang Yu, Giovanni Melandri, Anna C. Dittrich, Sebastian Calleja, Kyle Palos, Aparna Srinivasan, Emily K Brewer, Riley Henderson, Ciara Denise Garcia, Xiaodan Zhang, Bruno Rozzi, Andrea Eveland, Susan J. Schroeder, David Stern, Aleksandra Skirycz, Eric Lyons, Elizabeth A. Arnold, Brian D. Gregory, Andrew D. L. Nelson, Duke Pauli
Sissy E. Wamaitha, Ernesto J. Rojas, Francesco Monticolo, Fei-man Hsu, Enrique Sosa, Amanda M. Mackie, Kiana Oyama, Maggie Custer, Melinda Murphy, Diana J. Laird, Jian Shu, Jon D. Hennebold, Amander T. Clark
Vanesa Fernández-Majada, Jordi Comelles, Aina Abad-Lázaro, Verónica Acevedo, Anna Esteve-Codina, Xavier Hernando-Momblona, Eduard Batlle, Elena Martinez
Hong Jiang, Emilie Derisoud, Denise Parreira, Nayere Taebnia, Paulo R. Jannig, Reza Zandi Shafagh, Allan Zhao, Congru Li, Macarena Ortiz, Manuel Alejandro Maliqueo, Elisabet Stener-Victorin, Volker M. Lauschke, Qiaolin Deng
Tatsuya Tsukamoto, Ji Kent Kwah, Mark E. Zweifel, Naomi Courtemanche, Micah D. Gearhart, Katherine M. Walstrom, Aimee Jaramillo-Lambert, David Greenstein
Giada Rossignoli, Michael Oberhuemer, Ida Sophie Brun, Irene Zorzan, Anna Osnato, Anne Wenzel, Emiel van Genderen, Andrea Drusin, Giorgia Panebianco, Nicolò Magri, Mairim Alexandra Solis, Chiara Colantuono, Sam Samuël Franciscus Allegonda van Knippenberg, Thi Xuan Ai Pham, Sherif Khodeer, Paolo Grumati, Davide Cacchiarelli, Paolo Martini, Nicolas Rivron, Vincent Pasque, Jan Jakub Żylicz, Martin Leeb, Graziano Martello
Nagham Khouri-Farah, Emma Wentworth Winchester, Brian M. Schilder, Kelsey Robinson, Sarah W. Curtis, Nathan G. Skene, Elizabeth J. Leslie-Clarkson, Justin Cotney
Peter M Luo, Neha Ahuja, Christopher Chaney, Danielle Pi, Aleksandra Cwiek, Zaneta Markowska, Chitkale Hiremath, Denise Marciano, Karen K Hirschi, M Luisa Iruela-Arispe, Thomas J Carroll, Ondine Cleaver
Giada Rossignoli, Michael Oberhuemer, Ida Sophie Brun, Irene Zorzan, Anna Osnato, Anne Wenzel, Emiel van Genderen, Andrea Drusin, Giorgia Panebianco, Nicolò Magri, Mairim Alexandra Solis, Chiara Colantuono, Sam Samuël Franciscus Allegonda van Knippenberg, Thi Xuan Ai Pham, Sherif Khodeer, Paolo Grumati, Davide Cacchiarelli, Paolo Martini, Nicolas Rivron, Vincent Pasque, Jan Jakub Żylicz, Martin Leeb, Graziano Martello
Columbia University Department of Neuroscience, 2025
For many years, Parkinson’s disease (PD) research has predominantly focused on its well-known motor symptoms, such as tremors, rigidity, and bradykinesia. However, nonmotor symptoms, including anxiety, depression, and cognitive issues, have largely been overlooked, despite their significant impact on patients’ quality of life. These nonmotor symptoms often appear before motor dysfunction and can offer valuable insights into the progression of PD.
Kumayl Alloo, a research scholar at Columbia University’s Benson and Huntley Labs and the Icahn School of Medicine at Mount Sinai, is addressing this gap by investigating the complex interaction between the genetic and environmental factors that contribute to PD’s nonmotor effects on the brain.
“Our lab has been exploring how the LRRK2-G2019S mutation, a major genetic risk factor for PD, interacts with chronic stress, a well-known environmental risk factor, to influence nonmotor symptoms,” Alloo explained. “Our previous studies in mouse models exposed to both factors revealed behavioral and neurological changes, but we didn’t know which specific brain regions or synapses were involved. We understood the ‘what,’ but not the ‘where.’” This challenge became the cornerstone of Alloo’s research, which seeks to uncover the neural mechanisms responsible for these changes.
In their latest study (Guevara, Alloo, et al., 2024), Alloo and his team made significant progress by identifying how these risk factors interact in a sex-specific manner. Their research showed that the LRRK2 mutation and chronic stress together affected synaptic activity in areas such as the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and basolateral amygdala (BLA)—regions involved in emotional regulation and cognition. These alterations were linked to increased anxiety-like behaviors in male models, while female models displayed varying levels of resilience or susceptibility depending on the type of stress experienced.
These findings shed light on how genetic and environmental risk factors can disrupt brain circuits before motor symptoms appear, offering the possibility of earlier interventions. This work also sets the stage for future research into PD detection, classification, and treatment. “Now that we’ve pinpointed the areas involved, future therapeutic efforts can target these regions more effectively,” Alloo said.
An innovative and exceptional young scientist, already with over 15 peer-reviewed, funded research projects, books, abstracts, and journal publications to his name, Alloo’s contributions exemplify the importance of fostering early-career researchers to tackle pressing challenges in neurodegeneration. His work is helping to redefine our understanding of PD.
“My long-term goal is to become a physician-scientist, bridging the gap between research and clinical practice,” he says. “This unique combination allows me to address the clinical needs of patients while conducting research that directly informs those needs. By integrating bench-to-bedside approaches, where treatment and research mutually benefit one another, we can develop innovative cures and therapies.”
As Kumayl Alloo and his lab continue to deepen our understanding of Parkinson’s disease, their work demonstrates the power of combining academic research with clinical practice to tackle one of the most challenging neurodegenerative disorders of our time.
In their recent paper, Maia-Gil and colleagues explored whether and how nuclear properties can influence nuclear positioning in vivo. Their work revealed that in the densely packed retinal zebrafish neuroepithelium, nuclear deformability facilitates apical nuclear migration (Maia-Gil et al. 2024). Here, they share the science and the adventures that led to the development of this project.
What was already known?
The Norden Lab has been focused on understanding the cell and tissue biology behind zebrafish retinal development for 1.5 decades by now. The retina develops from a pseudostratified neuroepithelium, composed of a single, densely packed layer of highly elongated cells. Among other topics, the lab has been investigating a hallmark of such pseudostratified neuroepithelia which is apical nuclear migration before mitosis. This phenomenon is characterised by a fast and directed movement of nuclei toward the apical surface of the tissue. At the start of this project, we already knew:
Why nuclei migrate apically: their apical positioning before cell division ensures tissue integrity (Strzyz et al. 2015).
When this migration occurs: during the G2 phase of the cell cycle (Leung et al. 2011).
Schematic representing nuclear apical migration during the G2 phase of the cell cycle (Adapted from Yanakieva et al. 2019).
The big question: how to move through the crowd … and to get to the bar?
One evening, while the lab was out for a social gathering, we found ourselves facing a packed bar, and I was struggling to get my favourite drink – Porto Tónico. Determined to reach the bartender, we started brainstorming different ways to navigate through the crowd quickly and efficiently. In the middle of many creative (and impractical) ideas, someone jokingly suggested: “What if we could deform and squeeze through the crowd – just like nuclei do during apical migration?”
This offhand idea raised a novel question: Does nuclear deformability facilitate apical nuclear migration in the crowded retinal neuroepithelium?
Nuclei (grey) dynamics during zebrafish retina development. (Maia-Gil et al. 2024).
Our approach: stiffening nuclei and tracking their movement during organ development
We already knew that zebrafish retinal nuclei are highly deformable and express low levels of Lamin A/C (Yanakieva et al. 2019), a nuclear envelope protein with expression level that correlates with nuclear stiffness. To test our hypothesis that nuclear deformability helps apical migration, we increased nuclear stiffness by using a previously generated transgenic zebrafish line in which all nuclei overexpress Lamin A (Amini et al. 2022). With crucial support from our collaborators, we used atomic force microscopy (with Elias Barriga and Jaime Espina) and developed a mechanical model that represents confined nuclei as compressible droplets (with Anna Erzberger and Roman Belousov) to confirm that Lamin A overexpression indeed led to stiffer nuclei in the retinal neuroepithelium.
The run to the apical side
With this knowledge and our established tools, we used light-sheet microscopy to image zebrafish retinas and quantify apical nuclear migration in vivo. We aimed to answer several key questions:
Do stiffer, Lamin A overexpressing nuclei reach the apical side? Yes, but in contrast to control nuclei, stiffer nuclei take twice as long to cover equivalent distances. This delay occurs regardless of whether the surrounding nuclei are stiff or normal, suggesting that nuclear deformability facilitates migration in a cell-autonomous manner.
Does the deformability of surrounding nuclei affect apical migration? Yes! Control nuclei surrounded by stiffer nuclei also take longer and show less directed movement. This indicates that the mechanical properties of the environment influence nuclear migration.
Does increased nuclear stiffness impair apical migration in a less crowded epithelium? Here, the effect was less pronounced. Lamin A overexpression in the zebrafish hindbrain, a less crowded neuroepithelium, had only minor effects on apical nuclear migration. This suggests that the impact of nuclear stiffness depends on tissue packing.
Does nuclear stiffness affect other processes requiring cellular deformation? Yes! Control cells took longer to round up before mitosis when in a stiffer environment, showing that nuclear properties can influence mitotic entry in a non-cell-autonomous manner.
Together, these findings demonstrate that nuclear properties influence nuclear positioning and mitotic entry in a tissue-dependent manner during neuroepithelial development.
A personal developmental project…during revisions
My belly was growing, fatigue was setting in, and the time was ticking. The revision email arrived with a challenging to-do list. Priorities had to be redefined and our strategy adjusted. We needed more hands on the bench and had to dig deep into previous data. What could have been an erratic roller coaster turned into a successful and rewarding scientific adventure. I am grateful to have been surrounded by outstanding scientists who also advocate for woman in science. Their encouragement was invaluable – not only for the success of my PhD project but also for the development of the two most beautiful retinas I have ever seen.
References
1. Maia-Gil, M., Gorjão, M., Belousov, R., Espina, J.A., Coelho, J., Gouhier, J., Ramos, A.P., Barriga, E.H., Erzberger, A., and Norden, C. (2024). Nuclear deformability facilitates apical nuclear migration in the developing zebrafish retina. Current Biology 34, 5429-5443.e8. https://doi.org/10.1016/j.cub.2024.10.015.
2. Strzyz, P.J., Lee, H.O., Sidhaye, J., Weber, I.P., Leung, L.C., and Norden, C. (2015). Interkinetic Nuclear Migration Is Centrosome Independent and Ensures Apical Cell Division to Maintain Tissue Integrity. Developmental Cell 32, 203–219. https://doi.org/10.1016/j.devcel.2014.12.001.
3. Leung, L., Klopper, A.V., Grill, S.W., Harris, W.A., and Norden, C. (2011). Apical migration of nuclei during G2 is a prerequisite for all nuclear motion in zebrafish neuroepithelia. Development 138, 5003–5013. https://doi.org/10.1242/dev.071522.
4. Norden, C., Young, S., Link, B.A., and Harris, W.A. (2009). Actomyosin Is the Main Driver of Interkinetic Nuclear Migration in the Retina. Cell 138, 1195–1208. https://doi.org/10.1016/j.cell.2009.06.032.
5. Yanakieva, I., Erzberger, A., Matejčić, M., Modes, C.D., and Norden, C. (2019). Cell and tissue morphology determine actin-dependent nuclear migration mechanisms in neuroepithelia. Journal of Cell Biology 218, 3272–3289. https://doi.org/10.1083/jcb.201901077.
6. Amini, R., Bhatnagar, A., Schlüßler, R., Möllmert, S., Guck, J., and Norden, C. (2022). Amoeboid-like migration ensures correct horizontal cell layer formation in the developing vertebrate retina. eLife 11, e76408. https://doi.org/10.7554/eLife.76408.
Register now for the Young Embryologist Network meeting – Monday 19 May 2025 at the Francis Crick Institute.
Are you an early career researcher in developmental and stem cell biology? Then come to the 17th Young Embryologist Network Conference! Registration and abstract submission for talks and posters can be accessed here: YEN 2025 Registration form. Abstract deadline is the 13 April 2025.
YEN has a long history of enabling PhD students and early career researchers to share their research and network [1,2], as well as supporting the developmental biology research community [3]. Each year, YEN conferences are organised by students and postdoctoral researchers based in the UK. In recent years, the scope and reach of the YEN conference has grown significantly. We are committed to providing an open and free networking opportunity for developmental and stem cell biologists.
For YEN 2025 we again have a great line-up of speakers, with Nicolas Rivron from the Austrian Institute of Molecular Biotechnology (IMBA, ÖAW) giving the Sammy Lee Memorial Lecture on his work on blastocysts and in vitro embryo models. We will also welcome Peter Rugg-Gunn, Group Leader in Epigenetics of Human Development and Head of Public Engagement at the Babraham Institute (Cambridge UK) and Maud Borensztein, Group Leader at IGMM-Montpellier (France), who is working on X chromosome reactivation during germline development.
We are also pleased to announce this year’s Scientific Perspectives talks, which will focus on ‘Embryology at the frontiers of technology’ with Rob Tetley from Nikon Instruments and Simon Hanassab from Imperial College London, who is working on how AI can improve decision making in IVF.
PhD students and postdocs who would like to give a short talk or present a poster are invited to submit an abstract. We welcome international applications and have secured some funding to support travel grants. Please register using the form at forms.gle/fxtmNHjEziVTFprN6.
As always, we are very grateful to our sponsors including The Company of Biologists, 10X Genomics and Azenta, The Crick for hosting us and to the participants for attending.
Would you like to learn more about how to make your lab greener? We are excited to offer you insight into what sustainable action you can put into practice in the lab.
Jeroen Dobbelaere is our guest author for our newest series of blogs entitled “How to make labs more sustainable”. In this series, Jeroen will introduce you to useful advice and resources that can help you make your lab more environmentally- friendly. It will include aspects such as energy usage, lab equipment selection and procurement.
With Jeroen’s broad experience in both sustainability and academia, his blogs will be a great primer on how to combine these aspects. See more about Jeroen here.
As embryos develop, their cells perform two fundamental tasks: they divide to populate the developing organism, and they specialize into different cell types—skin cells, brain cells, and more—to carry out a variety of essential functions. In our paper, we set out to explore how the process of cell division influences the differentiation of various cell types during early development.
When I joined Allon Klein’s lab, the team had just published single-cell atlases of zebrafish and frog development (Wagner et al. and Briggs et al. 2018), offering a detailed map of cell states over several hours of embryonic development. Allon and I began brainstorming ways to use them to learn new biology beyond cataloging transcriptional states. We had long discussions on project directions and various fundamental developmental processes we could investigate—genome organization, metabolism, or cell division. As I started reading literature, cell division quickly stood out.
Due to its periodic nature, it has been hypothesized that cell division could act as a clock for developmental events. However, much of the literature does not support the universality of this hypothesis. For instance, studies in ascidian embryos showed that when cell division was blocked at the eight-cell stage, some cells still expressed muscle markers at the correct developmental time, suggesting that cell division was not required for commitment to the muscle lineage (Whittaker et al. 1973, figure below). While several similar studies had tested the impact of blocking division on a few marker genes, a systematic investigation into the role of cell division in forming all major cell types during early development was missing. So, we decided to do just that—in zebrafish embryos.
Zebrafish provided an ideal system for this question because their cells divide and differentiate rapidly in the first day of development (Figure below). Going into my first experiments, I expected to find at least some cell types whose differentiation would depend on active cell cycling. Alternatively, I imagined encountering intermediate “mixed” cell states which I could then follow up on for the rest of my PhD. But, to our surprise, all major cell types differentiated just fine without cell division.
For a while, I was stuck on how to move forward in the project. I spent nearly a year analyzing gene expression changes between control embryos and embryos arrested in the cell cycle. Two key patterns emerged:
Blood cells differentiated more slowly in arrested embryos, indicating a cell type-specific delay in differentiation.
Arrested embryos exhibited a characteristic transcriptional program related to cell cycle arrest that was global and independent of cell type.
While differentiation seemed largely unaffected, cell division also controls the proportions of cells across tissues and organs. We asked how blocking division influenced this. One possible outcome was that cell types that normally divide more frequently would be disproportionately reduced in arrested embryos. Alternatively, the embryos might activate a “compensation” mechanism to maintain normal cell proportions.
To answer this, we needed to estimate how many times each cell type has divided under normal conditions—a challenging problem. Emerging lineage tracing tools will likely solve this soon, but we took a computational approach, inferring cell division numbers from single-cell transcriptome data and lineage trees. As expected, cell types that typically divide the most were the most affected by division arrest. However, quantitatively, the effect was less severe than anticipated, suggesting some level of compensation.
Thus, while cell division is not necessary for differentiation, division influences the timing and proportions of cell types.
References
Whittaker, J. R. “Segregation during ascidian embryogenesis of egg cytoplasmic information for tissue-specific enzyme development.” Proceedings of The National Academy of Sciences 70.7 (1973): 2096-2100.
Wagner, Daniel E., et al. “Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo.” Science 360.6392 (2018): 981-987.
Briggs, James A., et al. “The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution.” Science 360.6392 (2018): eaar5780
Welcome to Development’s January newsletter. We’ll start by wishing all our readers a happy and productive 2025, which – as highlighted below – marks The Company of Biologists’ 100th birthday.
Celebrating 100 years of The Company of Biologists
Development’s publisher, The Company of Biologists, was founded in 1925 and this year marks our 100th anniversary. You can find out more about the history and ethos of this unique organisation in our January Editorial. We’ll be celebrating throughout the year with content in the journal, our community sites and on social media – check out the #100biologists hashtag on Bluesky and X to find out about some of the extraordinary scientists who’ve been associated with the Company over our long history. We’d also love to hear your stories – how has the Company supported you in your career? Please send us your ‘message in a bottle’ to let us know.
The centrepiece of our celebrations is the Biologists @ 100 conference, being held in Liverpool 24-27 March 2025. We’d love to see you there. The registration deadline is 28 February 2025.
Constructive Critics: Development’s approach to peer review
We all know that the peer review process isn’t perfect and here at Development we’re always trying to find ways to ease the path to publication without compromising our high standards. This Editorial summarises some of the things we’ve done in recent years, including our latest recommendation that authors should include a ‘Limitations’ section in their article – providing the opportunity for frank discussion of potential caveats of the work.
Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues
We are delighted to announce a call for papers for our 2025 special issue. Guest-edited by Meritxell Huch and Mansi Srivastava, working alongside our team of Academic Editors, this issue will focus on developmental processes beyond the embryo. Full details of the scope of the issue can be found on our website and you’re welcome to send us a presubmission enquiry if you’re unsure whether the scope of your work fits within this issue.
Pathway to Independence programme: call for applications
Are you a postdoc planning to go on the job market this year? Could you benefit from some mentorship, training and networking opportunities? If so, Development’s Pathway to Independence programme could be for you. Now in its third year, this competitive scheme aims to support postdocs as they seek their first independent position: we welcome applications from across the globe and look forward to growing our network of PI fellows.
The Company of Biologists’ Grants and Workshops: upcoming deadlines
Autonomous anteroposterior polarization in aggregates of mouse embryonic stem cells illustrates how alternative initial cell states between the embryo and the aggregates may converge onto similar fates.
The mitochondrial citrate carrier, SLC25A1, regulates trophoblast differentiation and placental development to safeguard embryonic heart formation.
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The latest issue of Development (vol 152 issue 2) features a Perspective article by Duygu Özpolat, Swathi Arur (one of Development’s Academic Editors), and Mansi Srivastava (currently serving as a Guest Editor for the journal). The piece represents their views and is not intended as a formal position statement of the journal, but much of what they write resonates strongly with my own opinions and with discussions I’ve had with the editors of the journal over the years.
Back when I was growing up as a developmental biologist, the tables of contents of journals like Development were full of papers with some variation on the title “Gene/protein X controls process Y in organ/organism Z”. Indeed, my first ever paper (proudly published in Development) essentially conforms to this formula. And getting those papers published in ‘top’ journals at that time (and since!) generally meant understanding that ‘control’ at a molecular level – what other genes or proteins does X interact with or regulate? This approach has been hugely important for our field, and we’ve made enormous progress in understanding the logic of developmental processes through delving into molecular mechanisms. But it’s not the only approach or level of understanding at which we can gain profound insights. As someone who’s always been interested in cellular and tissue-level behaviours, I’ve often felt this focus to be too narrow. Indeed, one of my mantras since joining the journal has been that “mechanistic understanding doesn’t necessarily mean molecular mechanistic understanding”. (The other, incidentally, is that “development doesn’t stop at birth” – which is why I’m personally delighted by our current special issue topic!).
It’s notable that, in the latest iteration of the journal’s Aims and scope, we actually removed the words ‘mechanism’ and ‘mechanistic’ from our description of the kinds of papers we seek to publish. That’s not to say we’re not interested in mechanistic work – of course we are! – it’s that we recognise that ‘mechanism’ is all-too-often conceived as being at the molecular/genetic level. Particularly with advances in 4D imaging and in measuring and manipulating forces, we can now gain significant insights into how developmental processes are orchestrated by studying cellular behaviours and without really worrying about what molecules are involved and we’d like those papers to find their natural home in Development. We also need to acknowledge the importance of foundational descriptive work, without which those interested in understanding ‘mechanism’ couldn’t even start their research.
Survey answers to the questions A “In your area of work, what is the most common interpretation of the term ‘mechanism’ as applied to research questions?” and B “When you assess work in your field, what do you look for in terms of a mechanistic understanding of development?”. Taken from Özpolat et al., 2025. The reversal in size of the words ‘Gene’ and ‘Cell’ in the two word clouds exemplifies the mismatch between common perception and personal views.
So, if you’re a referee reviewing a paper for Development (or, frankly, anywhere else!), I’d urge you to avoid asking yourself “does this paper provide new (molecular) mechanistic insights?” and instead to ask “how valuable are these findings for the field?”. I don’t think I can put it better than Duygu, Swathi and Mansi do in their article: “question reductionism, be open-minded about the approach used and the level of mechanism under study, and consider each study relative to what is already known in that system, assessing the potential of the work to advance knowledge”.
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