The Company of Biologists is organising an essay competition entitled “Innovative Ideas for the Future of Sustainable Events”.
Participants are invited to write an essay of maximum 1000 words to details how your idea will change the way we organise scientific events and will open the door to a new concept of organising events more sustainably in the next 10 years.
Prizes:
1st place: £250
2nd place: £150
3rd place: £100
The winning essays will be selected by the Sustainability Committee and featured on The Company of Biologists’ website.
This is a fantastic opportunity for anyone passionate about sustainability and writing. For more details, please visit our post here.
In this ‘Featured image’ post, we find out more about the story behind Allan Carrillo-Baltodano’s image, which was one of the runners-up in the competition.
Dancing actinotroch Allan Carillo-Baltodano Actinotroch larva of a phoronid worm with phalloidin shown in yellow and acetylated tubulin in magenta. Imaged with a Zeiss LSM 800 at 10 x magnification.
What is your background?
I did my undergrad at the University of Costa Rica, in Costa Rica. Early on, I biased my interests towards invertebrate zoology, and ended up doing an undergrad thesis on marine zooplankton of coral reefs. It was back then when I saw the beauty of marine invertebrate larvae. I have been studying evolution and development (EvoDevo) of marine invertebrates since — first, during my PhD in Néva Meyer’s lab at Clark University in Massachusetts (USA), and currently as a postdoc in Chema Martín-Durán’s lab at Queen Mary University of London in UK.
What are you currently working on?
I study how body plans of marine annelids develop, and try to understand how different modes of development in these and other animals could have evolved.
Can you tell us more about the story behind the image that you submitted to the image competition?
The image shows a larva of a phoronid worm. The larva is commonly known as actinotroch, and it is very conspicuous among other members of the zooplankton community because of the tentacles surrounding the head. To swim the larva propels itself using cilia (shown in the image in magenta) concentrated in a ciliary band on the posterior part of the larva. The big hoodie you see at the top will open slightly so that food can be captured in the mouth. One of the wonderful things of the plankton is that if you are lucky, you can find any stage of development of these and many other amazingly weird invertebrates.
What is your favourite technique?
I like mostly confocal microscopy, although if a sample is nice enough, you can get some very beautiful images with DIC microscopy as well.
What excites you the most in the field of developmental and stem cell biology?
The breakthrough in technologies has really opened the door for many of us who like to study development in unusual research organisms. In combination with the EvoDevo field being more open and the growing interest in comparative biology across many species and many scales, we are creating a great environment for anyone to make new discoveries.
Abstract submission to the Young Embryologist Network Conference closes this week on the 13th April 2025. Please share!
This is a great opportunity for PhD students and postdocs working on differentiation, stem cells, embryonic development, IVF or organoids to present a short talk or a poster. YEN2025 will take places at the Francis Crick Institute on the 19th May and is free to attend.
Exiting news! We have revived our tradition of the YEN Image Competition. Please submit your science images and art by the 1st May 2025 and follow us to get updates on where to vote!
Special thanks to Maddie Ryan, Charli Corcoran & Michaela Noskova Fairley for putting this digest together! If you would like to thank the Zebrafish Rock! team for their time & effort, you can buy us a strong cuppa at the link below. Every little bit keeps us caffeinated and motivated! We appreciate your support 🙂
Spotted a preprint in this list that you love? If you’re keen to gain some science writing experience and be part of a friendly, diverse and international community, consider joining preLights and writing a preprint highlight article.
Christina McNerney, Clayton P. Santiago, Kiara C. Eldred, Ian Glass, Tom A. Reh, Arturo Hernandez, Seth Blackshaw, Nathan D. Lord, Robert J. Johnston Jr
Giulia Di Muzio, Sarah Benedetto, Li-Chin Wang, Lea Weber, Franciscus van der Hoeven, Brittney Armstrong, Hsin-Jui Lu, Jana Berlanda, Verena Körber, Nina Claudino, Michelle Krogemann, Thomas Höfer, Pei-Chi Wei
Christopher Chan Jin Ji, Daniel Santos-Olivan, Marie-Christine Ramel, Juliana Sanchez-Posada, Priscilla Paizakis, Toby GR Andrews, Emily S Noel, Alejandro Torres-Sanchez, Rashmi Priya
Binbin Ma, Guanghui Yang, Jonathan Yao, Charles Wu, Jean Pinckney Vega, Gabriel Manske, Saher Sue Hammoud, Satrajit Sinha, Abhyudai Singh, Haiqing Zhao, Xin Chen
Tsz Long Chu, Ostap Dregval, Farasat Zaman, Lei Li, Xin Tian, Xin Liu, Dana Trompet, Baoyi Zhou, Jussi O Heinonen, Claes Ohlsson, Lars Sävendahl, Igor Adameyko, Andrei S Chagin
Tina Balayo, Sharna Lunn, Pau Pascual-Mas, Ulla-Maj Fiuza, Amruta Vasudevan, Joshua D. Frenster, Hannah Y. Galloon, Raquel Flores Peirats, Alfonso Martinez Arias, André Dias, David A. Turner
Beatriz Gomes-Silva, Marta Furtado, Marta Ribeiro, Sandra Martins, Maria Teresa Carvalho, Henrike Maatz, Michael Radke, Michael Gotthardt, Rosina Savisaar, Maria Carmo-Fonseca
Michelangelo Corcelli, Ellen Petzendorfer, Kate Hawkins, Filipa Vlahova, Catherine Caruso, Mehedi Mohammad Hasan, Katie Durrant, Anna David, Fleur S van Dijk, Pascale V Guillot
Jengmin Kang, Abhijnya Kanugovi, M. Pilar J. Stella, Zofija Frimand, Jean Farup, Andoni Urtasun, Shixuan Liu, Anne-Sofie Clausen, Heather Ishak, Summer Bui, Soochi Kim, Camille Ezran, Olga Botvinnik, Ermelinda Porpiglia, Mark Krasnow, Antoine de Morree, Thomas A. Rando
Caramai N. Kamei, William G. B. Sampson, Carolin Albertz, Oliver Aries, Amber Wolf, Rohan M. Upadhyay, Samuel M. Hughes, Heiko Schenk, Frederic Bonnet, Bruce W. Draper, Kyle W. McCracken, Denise K. Marciano, Leif Oxburgh, Iain A. Drummond
Marie Alonso, Pierre Prévost, Aline Potier, Pascal GP Martin, Yves Caraglio, Michael Nicolas, Michel Hernould, Christophe Rothan, Béatrice Denoyes, Amèlia Gaston
Ioannis Sarropoulos, Mari Sepp, Tetsuya Yamada, Philipp S. L. Schäfer, Nils Trost, Julia Schmidt, Céline Schneider, Charis Drummer, Sophie Mißbach, Ibrahim I. Taskiran, Nikolai Hecker, Carmen Bravo González-Blas, Niklas Kempynck, Robert Frömel, Piyush Joshi, Evgeny Leushkin, Frederik Arnskötter, Kevin Leiss, Konstantin Okonechnikov, Steven Lisgo, Miklós Palkovits, Svante Pääbo, Margarida Cardoso-Moreira, Lena M. Kutscher, Rüdiger Behr, Stefan M. Pfister, Stein Aerts, Henrik Kaessmann
Dang M. Nguyen, Sarah K. Monroe, Danielle N. Rendina, Kevin S. Boyd, Erika D. Rispoli, Olivia M. Wirfel, A. Brayan Campos-Salazar, Anna R. Araujo, Trisha V. Vaidyanathan, Virginia L. Keziah, Benjamin A. Devlin, Caroline J. Smith, Staci D. Bilbo
N. Zollo, G. Zaffagnini, A. Canette, G. Letort, C. Da Silva, N. Tessandier, J. Dumont, C. Blugeon, S. Lemoine, B. Wattellier, E. Böke, M. Almonacid, M.-H. Verlhac
Ruta Meleckyte, Wazeer Varsally, Jasmin Zohren, Jerry Eriksson, Tania Incitti, Linda Starnes, Amy Pointon, Ryan Hicks, Benjamin E. Powell, James M.A. Turner
Katelyn M. Cooper, Carly A. Busch, Alice Accorsi, Derek A. Applewhite, Parth B. Bhanderi, Bruno da Rocha-Azevedo, Abhijit Deb Roy, Joseph P. Campanale, Fred Chang, Jerry E. Chipuk, Lee A. Ligon, G.W. Gant Luxton, Austin J. Graham, Camila Hochman-Mendez, Imge Ozugergin, Zachory M. Park, Claire M. Thomas, Alex M. Valm, Hongxian Zhu, Rebecca S. Alvania
In this ‘Featured image’ post, we find out more about the story behind Julia Peloggia de Castro’s image, which was one of the runners-up in the competition.
Who’s active? The image depicts a zebrafish embryo at 9 hours post-fertilisation on a lateral view. Cells are stained with MitoTracker, which labels active mitochondria, and cell membranes are labelled in cyan with a EGFP transgenic membrane tag. Image was taken using a 20x objective on a spinning disk confocal microscope.
What is your background?
I got my bachelor’s degree at the University of São Paulo, in Brazil. I majored in Biological Sciences with a focus on genetics and molecular biology. I then pursued my PhD at the Stowers Institute for Medical Research in Kansas City (USA), where I studied zebrafish development and phenotypic plasticity under the mentorship of Dr. Tatjana Piotrowski. I am now a postdoctoral fellow at University of California, Los Angeles (USA) working with Dr. Heather Christofk.
What are you currently working on?
My current interests are in developmental metabolism, and how maternal metabolic states impact mouse embryonic development.
Can you tell us more about the story behind the image that you submitted to the image competition?
This image shows a zebrafish embryo after a few hours of development. One of my favorite things about zebrafish is how fast they develop, giving us the opportunity to watch it —and image it— in real time. This particular image was taken late at night in the laboratory while I was testing a reagent and optimizing imaging parameters before running a larger experiment later that week. The result was definitely worth staying late for!
What is your favourite technique?
I really appreciate any type of microscopy. From the foldscopes to confocal and electron microscopes. Looking at cells never gets old!
What excites you the most in the field of developmental and stem cell biology?
I think this is a very exciting moment in developmental biology research. The last decade has brought many technical revolutions and more fields are bridging towards developmental biology, generating new questions and new ways to approach them. This makes me think we are poised to discover new biological principles soon.
This is part of the ‘Lab meeting’ series featuring developmental and stem cell biology labs around the world.
Where is the lab?
Jennifer: You can find the Zenker Lab at the Australian Regenerative Medicine Institute (ARMI) at Monash University. We are super lucky to call Australia, to be exact Melbourne, our home. More information is available on our Zenker lab webpage or follow us on X (formerly Twitter) @LabZenker or on LinkedIn @JennyZenker.
Zenker lab group photo
Research summary
The transformation of an early mammalian embryo from a tiny soccer ball-like structure into a newborn with four limbs, a beating heart, and big bright eyes is one of the most remarkable and fundamental processes of life. Errors in these early steps in development can profoundly shape a person’s lifelong ability to carry out essential tasks for everyday living. Improving the efficiency of in-vitro fertilisation (IVF) treatments 1, 2, which are expensive, physically demanding and emotionally challenging, could set up parents-to-be for the best chance of a successful cycle when it is right for them. Our research vision is to implement a new cell biological paradigm for reproductive and regenerative medicine by uncovering the real-time movements inside single cells of the living embryo and human induced pluripotent stem cells (hiPSCs).
Inside the soccer ball-like embryo resides a handful of “all-rounder” cells, known as pluripotent cells, which can give rise to any type of cell in the adult body. Using 4D (3D plus time) live-cell imaging, our research is the first in the world to conclusively demonstrate that pluripotent cells have a highly organised internal road map composed of the microtubule cytoskeleton. This road map guides the asymmetric transport of RNAs and organelles in single cells of the living mammalian embryo as a decision-making process of their future fate, becoming either part of the embryo proper or extraembryonic tissues, for instance placenta 3, 4, 5, 6, 7. Together with national and international collaborators, we have been developing innovative tools and technologies. We generated the first in vitro model of human embryos, termed iBlastoids 8, producing the most spectacular images about this new Frontier in human stem cell biology, which will continue to be a world-leading approach for many years to come 9. Furthermore, we have been pioneering the application of innovative light-switchable regulators in living 3D physiological systems to allow the spatiotemporal manipulation of the microtubule network to control the potency and function of pluripotent cells non-invasively 3, 10.
Can you give us a lab roll call?
Jennifer: I will have to start here with Louise, who is our research assistant and keeps the lab running smoothly and always stocked up. Every other lab member has their own research project. I like to design them so that team members can work easily together. There is a group of people working on the living mouse embryo. Postdoc Hongbin and two undergraduate students, Tia and Ava, are unravelling how the localisation of RNA subtypes inside single cells of the embryo contributes to the development of a healthy embryo. The project of PhD student Manlin is closely linked to it, but instead of looking at RNA subtypes, she is looking at various organelles. PostDoc Jess and undergraduate student Aya are developing new tools to interfere with the transport of RNAs or organelles by manipulating the microtubule cytoskeleton with spatial and temporal precision. PhD student Tracey and undergraduate student Zhi Bie aim to understand how similar (or not) such processes are between mouse and human model systems. Then we have PhD student Oliver, graduate student Adam and undergraduate student Micaela who are all working with human induced pluripotent stem cells (hiPSCs) to translate our discoveries in reproductive biology to regenerative medicine. This area is now even more strengthened by our newest member PhD student Minoo who is working with both systems to understand how one cell can have the capacity to give rise to all cell types an adult body is made of.
Favourite technique, and why?
Jennifer: There is only one answer — live imaging. Being able to see in real-time how a new life starts developing is simply mind-blowing, better than any science-fiction movie or so you can watch at the movies.
Apart from your own research, what are you most excited about in developmental and stem cell biology?
Jennifer: Developmental and stem cell biology is the foundation for regenerative medicine, which is one of the newest fields of research. It is an amazing time to be involved in such a rapidly evolving field. it has an exceptional potential to help the wider society worldwide by improving our capabilities to more effectively treat a wide range of diseases. I might be bias but that’s the future.
How do you approach managing your group and all the different tasks required in your job?
Jennifer: There is one quote that says it all: “Fail to prepare, prepare to fail”. It is a lot indeed, but I love to plan and prepare, being on an exact time schedule and writing to-do lists sorted by priority and time requirements. But all this only works if there is an open, clear and effective communication across all lab members.
What is the best thing about where you work?
Oliver: The best thing about where I work is being part of a great team that works on interesting and important research. We are all working together to produce cutting-edge discoveries and there is a huge amount of satisfaction that comes from that. I am also lucky that working here gives me access to high-quality facilities and instruments, as well as interactions with exceptional colleagues.
Zhi Bie: For me, it’s the opportunity to attend various internal and external seminars hosted by ARMI. Although all the research groups belong to the same institution and share a general goal in regenerative medicine, I still have a limited understanding of areas outside my own group. The weekly institute seminars provide a welcoming, knowledgeable, and meaningful platform where staff and students can engage, share ideas, and gain novel perspectives from researchers with similar backgrounds.
Hongbin: I enjoy the active exchange of scientific ideas and findings here at ARMI, through weekly internal seminars, as well as regular external seminars that invite researchers from other universities or even other countries. These seminars not only provide insights into their scientific work but also offer opportunities to discuss career paths and professional development.
Adam: In my opinion, one of the best things about working at ARMI is the people I work with. Not only are the people friendly and enthusiastic to help you however they can, but I think it is really beneficial to share a workspace that is rich in diversity because you gain valuable insight into various cultural heritages and research backgrounds.
Tia: The community, both in the institute and in the lab, is extremely special. Specifically, I like how the community continuously views science in an almost child-like wonder whilst trying to do the best we can to discover new ways to help people. Furthermore, outside of the laboratory and seminars, there is a strong sense of support that extends past just science.
Micaela: The best thing about where we work is the community among the different labs, and the always smiling faces in the tea room.
What’s there to do outside of the lab?
Louise: I started playing badminton again when I joined the lab, encouraged by my supervisor Jenny Zenker with her attitude to sport and exercise. Now I am putting more effort into this sport outside the lab with more training and I am feeling much better physically and mentally. I think that is what Jenny wants to deliver via her non-scientific role outside the lab —triathlete.
Manlin: Melbourne is one of the best student cities in the world (QS World University Rankings). As the cultural and educational hub of Australia, it offers a vibrant academic environment, diverse communities, and a high quality of life. I truly enjoy studying and living here!
Zhi Bie: Melbourne is surrounded by the sea, and I love driving along the coastal roads at sunset. Chasing the light as it fades over the ocean gives me a sense of peace and clarity—it’s windy, cozy, and feels incredibly freeing. I’m also passionate about playing squash and badminton. The time I spend on the court brings a deep sense of focus and an exhilarating sensation of explosive muscle power.
Hongbin: Outside of the lab, I enjoy Melbourne’s beautiful mountains and beaches, which help me relax, recharge, and gather fresh energy for the work ahead.
Adam: As someone who has recently joined the lab from the UK, I enjoy spending my time outside of work indulging myself in everything Australia has to offer. Whether this be early morning runs along the Yarra River trying to spot wild kangaroos, road trips to explore the Great Ocean Road and stunning rainforest or simply lazy days at the beach enjoying the Melbourne sun — no two weekends are the same!
Tia: On site, the campus is filled with many spots to explore nature while you eat lunch that are truly stunning and relaxing. Off-site, there are some amazing beaches just a short drive from the lab that are great for decompressing after a day of running experiments.
Micaela: Outside of work there are beautiful coastlines to explore where you can go swimming, surfing or hiking. At the right time of the year you can even watch humpback whales migrating up the southeast coast of Australia, which is one of the most extraordinary things to witness.
References
[1] Jin H, Han Y, Zenker J. Cellular mechanisms of monozygotic twinning: clues from assisted reproduction. Hum Reprod Update. 2024;30(6):692-705. doi:10.1093/humupd/dmae022
[2] Jin H, Zenker J (2024) Seeing is believing: Visualising the Formation of Monozygotic Twins in IVF. J Reprod Med Gynecol Obstet 9: 180.
[3] Zenker J, White MD, Templin RM, et al. A microtubule-organizing center directing intracellular transport in the early mouse embryo. Science. 2017;357(6354):925-928. doi:10.1126/science.aam9335
[4] Zenker J, White MD, Gasnier M, et al. Expanding Actin Rings Zipper the Mouse Embryo for Blastocyst Formation. Cell. 2018;173(3):776-791.e17. doi:10.1016/j.cell.2018.02.035
[5] Hawdon A, Geoghegan ND, Mohenska M, et al. Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo. Nat Commun. 2023;14(1):2909. Published 2023 May 30. doi:10.1038/s41467-023-38436-2
[6] Hawdon A, Aberkane A, Zenker J. Microtubule-dependent subcellular organisation of pluripotent cells. Development. 2021;148(20):dev199909. doi:10.1242/dev.199909
[8] Liu X, Tan JP, Schröder J, et al. Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature. 2021;591(7851):627-632. doi:10.1038/s41586-021-03372-y
[9] Palacios Martínez S, Greaney J, Zenker J. Beyond the centrosome: The mystery of microtubule organising centres across mammalian preimplantation embryos. Curr Opin Cell Biol. 2022;77:102114. doi:10.1016/j.ceb.2022.102114
[10] Greaney J, Hawdon A, Stathatos GG, Aberkane A, Zenker J. Spatiotemporal Subcellular Manipulation of the Microtubule Cytoskeleton in the Living Preimplantation Mouse Embryo using Photostatins. J Vis Exp. 2021;(177):10.3791/63290. Published 2021 Nov 30. doi:10.3791/63290
A critical function of blood vessels is the transportation of plasma, blood cells, nutrients, and metabolites efficiently across the body. The formation and maintenance of blood vessels as hollow tubes is thus important for their function and is a research interest in our lab. One long-standing question in this subject is how apical membranes expand at luminal patches, which form between endothelial cells, at the initial phase of lumen formation. We questioned whether this could occur through physical forces generated from within the luminal patch that would drive the expansion of apical membranes to form a bigger lumen. This led to the hypothesis that endothelial cells may expel water at its apical surface into the luminal space to build up hydrostatic pressure that would consequently inflate the lumen. While we were exploring this idea, an scRNAseq screen in my lab identified two endothelial water channels, aqp1a.1 and aqp8a.1, to be differentially expressed within blood vascular networks of the developing zebrafish embryo. While aqp1a.1 mRNA is ubiquitously expressed in all blood vessels, aqp8a.1 mRNA expression is confined to the posterior trunk vessels and in the ventral regions of intersegmental vessels (ISVs). We therefore speculated that these two Aquaporins may have distinct roles in blood vessel formation and function.
Igor, the first author of the paper, subsequently generated zebrafish mutants using CRISPR/Cas9 to investigate the function of Aqp1a.1 and Aqp8a.1. Our initial analysis was focused on determining whether blood vessel lumens formed normally in aqp1a.1 and aqp8a.1 mutants. To address this, we performed microangiography experiments to examine lumen patency at 2 and 3 days post fertilisation (dpf), after trunk vessels have lumenised. This analysis showed a decrease in the number of ISVs that are fully perfused and an increase in the number of partially perfused ISVs (Fig. 1), which supported our hypothesis that Aquaporin-mediated water flow may have a role in lumen formation. However, we needed to exclude the possibility that the decrease in fully perfused ISVs may have arisen from a defect in an earlier phase of ISV formation. We therefore examined sprouting angiogenesis in aqp1a.1 and aqp8a.1 mutants. This took a long time as we needed to cross three mutant zebrafish lines (aqp1a.1-/-, aqp8a.1-/-and aqp1a.1-/-;aqp8a.1-/-) to a transgenic endothelial reporter line to visualise endothelial cell shape and behaviours. Eventually, through time-lapse live imaging, we discovered that endothelial tip cells lacking endothelial Aquaporins take longer to emerge from the dorsal aorta (or not at all), generate fewer membrane protrusions and migrate more slowly, thus impairing sprouting angiogenesis1. This was an unexpected finding since it is a commonly held perception that endothelial cell migration depends predominantly on the remodelling of actin cytoskeleton. Our findings instead implicate Aquaporin-mediated water flow as an alternative mechanism of endothelial cell migration in vivo, and the defects in lumen perfusion observed is secondary to incomplete ISV formation.
Figure 1. Deletion of endothelial aqp1a.1 and aqp8a.1 decreases the number of fully perfused intersegmental vessels (ISVs). (A) Microangiography was performed in 2 dpf wildtype, aqp1a.1-/-, aqp8a.1-/-or aqp1a.1-/-;aqp8a.1-/- zebrafish to fill and visualise lumenised blood vessels with dextran tetramethyl rhodamine (2000 kDa). Arrows, partially perfused ISVs. *, unperfused ISVs. Scale bar, 50µm. (B) Quantification of ISV perfusion in wildtype and aqp1a.1-/-;aqp8a.1-/- embryos at 3 dpf.
How do we demonstrate that Aquaporins mediate water flow in endothelial tip cells in vivo?
Aquaporins are widely known to increase water permeation by allowing water to flow across the plasma membrane up an osmotic gradient2. However, we did not know in which direction water flows as endothelial tip cells migrate. This was (and still is) a technical challenge since there is no available method to track water flow inside cells in a living organism. We thus attempted to address whether the loss of Aquaporin function would lead to changes in cytoplasmic viscosity by tracking (Video 1) and calculating the diffusion coefficient (Fig. 2) of genetically encoded multimeric nanoparticles, which self-assemble into spherical particles with a diameter of 50nm (50nm-GEMs)3. Unfortunately, we were unable to observe a difference in 50nm-GEM mobility between wildtype and aqp1a.1-/-;aqp8a.1-/- endothelial tip cells. Still, this did not necessarily mean that Aquaporins do not mediate water flow in endothelial cells since the diffusion coefficient of particles depends on their size4. In our experiment, the 50nm-GEMs may not be sensitive enough to detect small changes in cytoplasmic viscosity that is altered by water influx or efflux, or that the changes in viscosity may be confined to local regions of the cell. We next resorted to measuring tip cell volume, with the assumption that cytoplasmic volume would increase if Aquaporins mediate water influx or decrease if they mediate water efflux. Using this approach, we found that the cytoplasmic volume of tip cells decreased when both Aqp1a.1 and Aqp8a.1 were depleted; conversely, tip cell volume increased when Aqp1a.1 was overexpressed. Coupled with a reduction in tip cell elongation in aqp1a.1-/-;aqp8a.1-/- embryos, we concluded that Aquaporins mediate water influx into tip cells and in doing so, increase cytoplasmic hydrostatic pressure.
Video 1. Single particle tracking of 50nm-GEMs expressed in endothelial tip cells of wildtype and aqp1a.1-/-;aqp8a.1-/- embryos during ISV formation at 1 dpf. This experiment was done in collaboration with Liam J. Holt (NYU), Sameer Thukral (RIKEN BDR) and Yu-Chiun Wang (RIKEN BDR).Figure 2. Diffusion coefficient of 50nm-GEMs expressed in endothelial tip cells of wildtype and aqp1a.1-/-;aqp8a.1-/- embryos during ISV formation at 1 dpf.
What controls the direction of water flow?
That there is directed water flow into tip cells points towards the generation of an osmotic gradient by endothelial tip cells. Upon one of the reviewers’ suggestions, we investigated whether the anion channel, SWELL1 (also known as LRRC8A), may generate an osmotic gradient across the cell membrane to control water flow. To our surprise, chemical inhibition of SWELL1 phenocopied many of the defects found in aqp1a.1-/-;aqp8a.1-/- zebrafish including decreased membrane protrusions, migration velocity and ISV length. All in all, our work on endothelial Aquaporin function uncovered a novel role of osmotic pressure-driven water inflow and increased hydrostatic pressure in driving endothelial tip cell migration and sprouting angiogenesis in vivo1.
These new findings took me back to my post-doctoral work more than 10 years ago, when I discovered that endothelial tip cells continued to migrate, albeit more slowly, after the inhibition of actin polymerisation and in the absence of filopodia5. (This finding was another surprise as it challenged the previously held dogma that filopodia are necessary for polarised tip cell migration.) Curiously, tip cells were able to generate lamellipodia-type membrane protrusions under the low dose of Latrunculin B (Lat. B) treatment used to inhibit filopodia formation. Back then, I had assumed that the low dose of Lat. B used did not inhibit all actin polymerisation events so that some actin-based membrane protrusions could still be generated to drive the slower migration observed. However, our new results suggested that local increases in hydrostatic pressure in the cytoplasm could instead be the driving force for the observed residual migration. To support this, we inhibited both actin polymerisation and hydrostatic pressure by treating aqp1a.1-/-;aqp8a.1-/- embryos with Lat. B and discovered that tip cell migration and ISV formation were more severely impaired compared to their individual inhibition. This final experiment cemented the conclusion that endothelial tip cells employ two modes of migration – actin polymerisation and hydrostatic pressure – to ensure robust sprouting angiogenesis in physically confined tissues.
In sum, the journey behind our paper is one of twists and turns with a revisit of a past observation. Such discovery-based science filled with unexpected findings is what makes research exciting, and I look forward to uncovering more surprises in endothelial cell behaviours!
References:
1. Kondrychyn, I., He, L., Wint, H., Betsholtz, C. & Phng, L.-K. Combined forces of hydrostatic pressure and actin polymerization drive endothelial tip cell migration and sprouting angiogenesis. eLife13, RP98612 (2025).
2. Agre, P. et al. Aquaporin water channels – from atomic structure to clinical medicine. J. Physiol.542, 3–16 (2002).
3. Hernandez, C. M., Duran-Chaparro, D. C., Eeuwen, T. van, Rout, M. P. & Holt, L. J. Development and Characterization of 50 nanometer diameter Genetically Encoded Multimeric Nanoparticles. bioRxiv 2024.07.05.602291 (2024) doi:10.1101/2024.07.05.602291.
4. Sakai, K., Kondo, Y., Goto, Y. & Aoki, K. Cytoplasmic fluidization contributes to breaking spore dormancy in fission yeast. Proc. Natl. Acad. Sci.121, e2405553121 (2024).
5. Phng, L. K., Stanchi, F. & Gerhardt, H. Filopodia are dispensable for endothelial tip cell guidance. Development140, 4031–4040 (2013).
What is this? This video shows early stages of the embryonic development of the sea anemone Nematostella vectensis. In green, you can see the dynamic localization of the β-catenin protein carrying a fluorescent tag. β-catenin is a crucial molecule during embryogenesis, serving a dual role: structurally, it helps cells stick together; functionally, it enters cell nuclei to regulate gene expression. In this video, you can clearly observe glowing cell boundaries and the nuclear translocation of β-catenin in specific embryonic cells at specific developmental stages.
Where can this be found? In the wild, Nematostella vectensis inhabits shallow coastal waters along North America’s Atlantic coast. Today, it is a popular model organism in developmental biology labs worldwide. This specific fluorescent β-catenin-tagged Nematostella line was developed at the Department of Neuroscience and Developmental Biology, University of Vienna (Austria).
How was this taken? We used CRISPR/Cas9 genome editing to insert a GFP (Green Fluorescent Protein) sequence into the Nematostella β-catenin gene. After injecting around 35,000 embryos, we successfully identified one male carrying the correct insertion in the germ cells. This allowed us to establish first a heterozygous F1 and then a homozygous F2 generation with “glowing β-catenin” in all cells, enabling detailed developmental imaging. For imaging, embryos were gently immobilized in low-melting agarose and filmed live using a spinning disk confocal microscope at the Medical University of Vienna, with valuable support from the Adameyko lab.
Why should people care about this?
Nematostella belongs to Cnidaria (corals, sea anemones, and jellyfish), a sister group to Bilateria (insects, worms, sea urchins, and humans). In bilaterians, β-catenin signaling activates the formation of the endomesoderm, which soon splits into an endoderm giving rise to the gut tube and its derivatives, and mesoderm forming muscles, reproductive organs, and more. For over two decades, scientists assumed β-catenin had a similar function in cnidarians.
Our study challenges previous assumptions and provides new insights into how animal developmental mechanisms evolved. Upon careful observation, you will notice that in the early embryo, β-catenin enters cell nuclei on one side of the embryo, while later, endomesodermal cells start to invaginate on the opposite side of the embryo, forming its gut. Combined with the existing gene knockdown data, this shows that β-catenin does not specify the endomesoderm in Nematostella, as previously thought, but rather protects non-endomesodermal cells (ectoderm) from becoming the endomesoderm. This unexpected finding highlights an important evolutionary shift, suggesting that using β-catenin to specify the endomesoderm in the embryo was an evolutionary innovation of Bilateria.
At the end of each month, I pick the same month from a random year from the past 15 years of the Node, and take a look at what people were talking about back then.
Kim Cooper is one of the most prolific authors on the Node. Check out her posts between 2010 and 2012 about her adventures in China collecting jerboa embryos, and what research questions we can answer by studying the adorable creature.
Image competitions are always a crowd favourite. To accompany the Biologists @ 100 conference, we’ve recently partnered with FocalPlane to run an image competition. Check out the results of the competition.
To add or not to add ‘stem cells’ into BSDB’s name
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