Enthusiastic about science communication and looking for a chance to broaden your writing experience alongside your research activities? The Node, our community site for developmental and stem cell biologists, is looking to appoint three correspondents who will play a key role in developing and writing content over the coming year.
As part of a small cohort, you will have the chance to engage with fellow researchers and scicomm enthusiasts as you work together to plan and generate fresh content. You will also gain insight into the publishing industry through meetings with our in-house Editors, Community Managers and Science Communications Officer, and receive regular feedback on your writing. You can find a writeup on our workshop on conducting interviews on our sister site, preLights.
We will help raise your profile as a researcher and science communicator and are also happy to support you by contributing towards conference attendance costs relating to the role, providing reference letters, or in other ways.
You will be expected to contribute around six posts over the course of the year – this could involve creating your own blog series around a theme of your choice, reporting on the latest exciting developments in developmental and stem cell biology, interviewing inspiring scientists, or writing about conferences and other events. We are also open to any other ideas you might have as we would like to shape a programme that both appeals to your interests and benefits the research community.
Please note, we are also recruiting correspondents for FocalPlane, so when applying you will have the option of choosing to apply for the Node, FocalPlane or both.
We encourage applications from all individuals regardless of sexual orientation, gender identity or expression, religion, ethnicity, age, neurodiversity or disability status. We also welcome applicants from a range of geographic locations.
Please get in touch with us if you have any questions about the programme at thenode@biologists.com
A recent paper was published in Developmental Cell, titled “Mitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus”1. The researchers find that a mitochondrial membrane leak actives Hif-1α, which is sufficient to induce the Organizer and activate Wnt reporters. They propose that mitochondrial leak metabolism could be a general mechanism for activating Hif-1α and Wnt/β-catenin signalling. We caught up with the first author, Alexandra MacColl Garfinkel, PhD, to learn more about the story behind the paper.
How did you come to join the Khokha lab?
When I got to Yale University to start my PhD, I wanted to work in a setting that empowered independent and explorative science and used a well-established model and experimental framework. The Khokha lab provides such a wonderful space to do this. By utilizing available human congenital heart defect databases, and the well-established Xenopus model organism, students and post-docs can identify potentially important genes for human development and quickly screen for functional conservation in Xenopus. I was also deeply motivated by the underlying philosophy of Dr. Khokha’s lab, which is rooted in a commitment to provide discoveries made in the lab to physicians who work directly with families struggling with the realities of birth defects. Discoveries made in the lab can provide information to families about why this type of defect occurs and can inform genetic testing that is done before conception or for in vitro fertilization procedures.
Because most genes do not have well defined roles in development, this lab framework leads to an amazing diversity of focuses and discoveries. This can be challenging, as everyone in the lab is working on something different, learning as they go; but it’s also an incredible asset. Everyone uses the same tools to begin their projects, which means a lot of intra-lab collaboration. It also breeds an incredibly supportive learning environment. Everyone becomes a teacher in the lab, and lab meetings are exceptionally diverse and interesting. It is also an environment that encourages inter-lab and inter-departmental collaborations. As students and post-docs delve deeper into the molecular mechanisms of the gene, pathway, or cellular process they are studying, reaching out to experts to learn new techniques and theories becomes crucial! This really attracted me to the lab.
How did the project get started?
My project began with the study of the gene LRPPRC, identified in a patient with congenital heart defects. I quickly found data in the literature that patients with mutations in LRPPRC are often diagnosed with French Canadian Leigh Syndrome or related metabolic diseases. However, I also found that some of these patients have a variety of structural birth defects. LRPPRC is a known RNA binding protein critical for the maintenance of the electron transport chain (ETC) and ATP synthase. So, the metabolic phenotypes made sense. But based on the other patient data, I was interested in a possible role of LRPPRC in embryonic patterning.
By using the CRISPR/Cas9 gene editing system, I knocked down this gene in Xenopus and found a significant number of heart and craniofacial defects, as well as more severe neural tube patterning defects. The neural tube and broad patterning defects suggested an early role for lrpprc in development. I looked at patterning markers throughout development and eventually found that the earliest defects occur at gastrulation. These gastrulation defects are caused by abnormal mesoderm specification, specifically the expansion of the Spemann-Mangold Organizer. I was shocked. I had expected to find a loss-of-function phenotype, associated with the disruption of mitochondrial ETC and ATP synthase functions. I had assumed that mutating this gene would cause a loss of cell fate specification or even cell death due to a decrease in energy production or increase in autophagy. But instead, I found this incredible shift in mesodermal cell fate specification, suggesting there were metabolic mechanisms driving cell fate decisions.
What was known about the establishment of the Spemann-Mangold Organizer and the role of mitochondria metabolism in Organizer specification before your work?
The Organizer is an evolutionarily conserved tissue that is named for its ability to “organize” pluripotent embryonic stem cells into the structures of the primary body axis. In 1924, Hans Spemann and Hilde Mangold first identified the Organizer and showed its capacity to instruct the fate and organization of nearby cells. By transplanting a pigmented newt embryo “organizer” into a non-pigmented newt embryo, they were able to track the transplanted cells and confirm their capacity to organize the host-tissue into a second, ectopic, embryonic body.2
Since the advent of genetic cloning, a handful of signaling pathways have been investigated for their role in establishing the Organizer. In particular, the canonical Wnt/β-catenin signaling pathway stimulates the expression of key Organizer genes. β-catenin is stabilized in the dorsal region of the developing embryo. It drives Organizer gene expression there and eventually establishes dorsal and neural cell lineages. However, before the field of developmental biology exploded with genetic tools, developmental biologists in the early 20th century thought that metabolism could be involved in the Organizer’s function. This has mostly been forgotten, as the progression of developmental biology became increasingly defined by the identification of powerful genetic signaling cascades. Looking back though, it is interesting to see how even in the 1930’s and 1950’s this idea was percolating.
At the time, developmental biologists were trying to understand what signal could emanate from the Organizer to communicate with surrounding cells and instruct them so thoroughly. We now know that BMP inhibitors are expressed in the Organizer and are secreted to nearby cells. However, these early studies hit upon something intriguing. Although controversial due to the difficulty of reproducibility, some scientists including Norma Ornstein and John Gregg found that dorsal explants from amphibian embryos consume more oxygen than ventral explants3. There was a lot of speculation about how this might be related to signaling from the Organizer, but not about how this might relate to the establishment of the Organizer itself.
Excerpts from Norma Ornstein and John Gregg’s 1952 paper titled “Respiratory Metabolism of Amphibian Gastrula Explants.” Their experiments showed a respiratory gradient that is highest in dorsal Organizer explants of gastrula embryos.
Can you summarize the paper’s key findings?
Disrupting oxidative phosphorylation, by genetic or environmental manipulation (hypoxia, Oligomycin), results in the expansion of the Organizer by upregulating Hif-1α.
Hif-1α overexpression leads to an expansion of the Organizer; knockdown of Hif-1α inhibits the expansion of the Organizer induced by mitochondrial manipulations or β-catenin overexpression.
Hif-1α acts downstream from β-catenin to establish Organizer gene expression and can induce Organizer specification even in the context of β-catenin knockdown.
Respiration in the Organizer is significantly higher than in the ventral mesoderm, suggesting Hif-1α is activated there despite functioning mitochondria. In fact, a functional ETC seems to be necessary for Organizer specification in wildtype embryos. This is due to the c-subunit of ATP Synthase acting as a mitochondrial membrane leak, which drives up ETC activity and increases oxygen consumption.
Targeted expression of the c-subunit of ATP Synthase can induce an ectopic Organizer in any region of the embryo and can result in a second embryonic head and body axis. This effect is dependent on Hif-1α and occurs downstream of β-catenin.
Overall, our work suggests that mitochondrial leak metabolism could be a general mechanism for activating Hif-1α and Wnt/β-catenin-target gene expression. It is also incredibly cool to answer an almost 75-year-old question and finally know why the Organizer uses more oxygen than other tissues!
(1) Regional oxygen consumption measured in whole, live embryos, the Organizer tissue is highly aerobic, consuming 20% more oxygen than ventral mesoderm. (2) Overexpression of ATP Synthase c-subunit mRNA is sufficient to induce a second Organizer and body axis.
Were you surprised to find that Hif-1α is sufficient to expand the Organizer cell fates in normoxia?
When I first overexpressed Hif-1a, and saw such a clear expansion of the Organizer, I was stunned and relieved. It was a major puzzle piece falling into place. I had been trying to make sense of why β-catenin was not increased in lrpprc CRISPR mutants. When you lose β-catenin, you lose Organizer specification completely, and when you overexpress it, you get an expansion or duplication of the Organizer, so I was expecting β-catenin to be driving the phenotype in the mutants. Because of the role of Lrpprc in mitochondrial maintenance, I had made a list of possible metabolic proteins to manipulate to see if I could recapitulate this phenotype. With the Hypoxia data we obtained in collaboration with Dr. Andrea Wills at the University of Washington, and from helpful conversations with her, I started with Hif-1α and saved a lot of time!
In terms of being surprised about the normoxia situation – honestly, I think I was so focused on the data, and focused on getting to a point where I deeply trusted my findings, that it didn’t strike me as that odd. There is something magical about being a PhD student setting out into a new field, especially because you come in with very few pre-conceived notions. I read so much about Hif-1α in a range of contexts and from what I learned it seemed pretty reasonable that something could be going on to stabilize HIf-1a in the embryo. In the end, biology is what it is, whether we understand the nuances or not. In the case of Hif-1a, I trusted the data, and used the amazing work already published by others to start making sense of the results!
Can you postulate about how Hif-1a is activated?
I have a few ideas about this. Hif-1α is dynamically regulated by so many signaling pathways and molecules. Obviously, you have the oxygen piece, then there are other factors like a-Ketoglutarate vs Succinate/Fumarate, pyruvate, and lactate, that are involved in regulating the activity of the prolyl hydroxylase domain (PHD) proteins that target Hif-1α for degradation; there are genetic regulators and growth factor signaling pathways that interact with Hif-1α. Then there are the direct interactions that have been described between Hif-1α and β-catenin, TCF/LEF, YAP1, and more. I think that in the context of mitochondrial membrane leak, regional increases in lactate and pyruvate could result in their competitive binding to PHDs and inhibit Hif-1α degradation. It is also possible that the increase in oxygen consumption produces high ROS levels which can inhibit PHD activity. Additionally, I saw an increase in regional mRNA levels in the Organizer and dorsal ectoderm, suggesting possible regulation at the transcription and/or translation levels. We are currently exploring these possibilities and I am excited for what is to come.
Did you have any particular result or eureka moment that has stuck with you?
Oh my, I feel like there were so many. During this work, I often felt like I was in the dark, following the dim light of my data, which sometimes felt like it was taking me in circles. I had a LOT of opportunities to practice trusting my data, even though I couldn’t see where it was leading me. And then there would be these flares of light, from a new result, or from reading a paper, and something would click, and I would jump 10 steps ahead. The whole project was truly an incredible learning experience.
I know I should probably stick to one, but I really couldn’t choose between these!
I have to say again, that the effect of overexpressing Hif-1α in the early embryo and getting such a striking Organizer phenotype was profound. It got us on track to begin understanding the mechanism. For me, it was the western blot I did to confirm Hif-1α is upregulated in lrpprc CRISPR mutants that really changed the game! That was when I did the experiments to confirm that losing Hif-1α rescues the lrpprc Organizer phenotype and I felt like I could begin sinking my teeth into the problem of what Hif-1α is doing early in development.
Seeing that Hif-1α can rescue the Organizer in β-catenin depleted embryos – I was absolutely shocked.
Going to London to perform regional Oxygen-consumption experiments in live embryos was such a privilege and a treat, then to find that the Organizer consumes more oxygen than other tissue blew me away. At the time I was such a novice in thinking about metabolism. Thank God for Dr Jonas and Dr Alavian – they laughed kind heartedly at my look of utter astonishment when we saw the result. They suspected what was going on immediately and helped me frame the concept of physiologically useful mitochondrial membrane leak. Seeing that the c-subunit leak could induce an ectopic body axis and Organizer was an incredible finale to this work.
In the context of β-catenin depletion, overexpression of Hif-1α can re-establish the Organizer.
And the flip-side: were there any moments of frustration or despair? What got you through?
Again, so many. Especially early on. I got the lrpprc ‘expanded Organizer’ phenotype and was so stumped because β-catenin wasn’t up. It took patience, creative experimenting, reading, and good conversations. When I read the 2017 papers that came out of Dr. Olivier Pourquié’s4 and Dr. Alexander Aulehla’s5 labs on glycolysis and cell fate specification during somitogenesis, it was huge. I finally felt like someone else was in the dark with me, shedding light on what could be going on. Even though our paper doesn’t focus on glycolysis, just being able to read about metabolism being involved in developmental cell fate and patterning was so helpful. Up until then, there was so little out there! Building out a new field of intersectional biology is difficult. It can feel lonely and frustrating, but also so exciting. I am deeply grateful for the people I’ve found along the way who have been exploring and defining the burgeoning field of developmental metabolism. For example, I just went to an EMBO Workshop at the EMBL in Heidelberg called “Developmental metabolism: Flows of energy, matter, and information.” It was incredible to see the diversity of backgrounds and fields represented by this excited group of people, all of them ready to collaborate to continue building out this field.
What is next for this story?
I am currently working with Dr. Jonas in the Endocrinology Department at Yale Medical School, delving deeper into the molecular mechanisms of how c-subunit, Hif-1α, and β-catenin collaborate to regulate embryonic patterning using mice and human stem cell models. I love this work and am so excited to continue learning about the mitochondria and metabolism side of things from Dr. Jonas. She has an incredible lab and skill set and I have learned so much from her already. In my own lab in the future, I hope to use my discoveries as a proof-of-concept to define other mechanisms that lie at the intersection of metabolism and known developmental pathways. I believe that exploring this intersection is crucial for the field developmental biology, but also for our understanding of how complex multicellular life evolved and diversified. I am so excited for what’s to come and to continue building and investigating the field of developmental metabolism!
Cited in this article:
1. MacColl Garfinkel, A., Mnatsakanyan, N., Patel, J.H., Wills, A.E., Shteyman, A., Smith, P.J.S., Alavian, K.N., Jonas, E.A., and Khokha, M.K. (2023). Mitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus. Dev Cell. 10.1016/j.devcel.2023.08.015.
2. Spemann, H., and Mangold, H. (1924). über Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren. Archiv für Mikroskopische Anatomie und Entwicklungsmechanik 100, 599-638. 10.1007/bf02108133.
3. Gregg, J.R., and Ornstein, N. (1952). Anaerobic Ammonia Production by Amphibian Gastrulae Explants. Biological Bulletin 102, 22-24. 10.2307/1538619.
4. Oginuma, M., Moncuquet, P., Xiong, F., Karoly, E., Chal, J., Guevorkian, K., and Pourquie, O. (2017). A Gradient of Glycolytic Activity Coordinates FGF and Wnt Signaling during Elongation of the Body Axis in Amniote Embryos. Dev Cell 40, 342-353 e310. 10.1016/j.devcel.2017.02.001.
5. Bulusu, V., Prior, N., Snaebjornsson, M.T., Kuehne, A., Sonnen, K.F., Kress, J., Stein, F., Schultz, C., Sauer, U., and Aulehla, A. (2017). Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development. Dev Cell 40, 331-341 e334. 10.1016/j.devcel.2017.01.015.
Jan Żylicz: Our primary focus is on unravelling the intricate molecular mechanisms through which chromatin and metabolism regulate early mammalian development. The team explores fundamental questions such as how global changes in metabolism lead to specific outcomes, the causal relationship between chromatin and gene expression alterations during lineage specification, and the biological significance of the coupling between metabolism and epigenetics.
Lab photo
Lab roll call
Sandra Bages Arnal: Lab Manager – I take care of the general things in the lab, like ordering, organization, mice colony management, etc. And I help people with their projects when needed.
Arnau Casoliba Melich: PhD student – I study the role of metabolism in promoting and maintaining the trophoblast lineage in mouse models using degron systems and CRISPR interference.
Antar Drews: PhD student – My interest lies in uncovering novel epigenetic regulators of lineage fate in the early human embryo, with a particular focus on the trophectoderm.
Eleni Kafkia: PostDoc – My scientific interests lie in understanding the metabolic architecture routings during pluripotent state transitions and how these are specifically intertwined with chromatin alterations. To elucidate this, I am employing a combination of 13C-isotope metabolic flux analyses, chemoproteomic profiling and CRISPRi/a technologies.
Viktoria Lavro: PhD student – I am using single-cell sequencing techniques to investigate the causes behind embryo failure and the fidelity of in vitro models in recapitulating key features of development.
David Pladevall Morera: PostDoc – I use CRISPR interference and high-throughput microscopy to decipher the role of metabolic enzymes in regulating chromatin and cell states during early embryonic development, specifically at the stage of embryo implantation.
Nikolaos Stamidis: PhD student – I am using in vivo and in vitro approaches to understand the role of histone acetylation in early mouse development, especially with regards to regulation of chromatin and gene expression.
Karlien van Nerum: PhD student – I am trying to understand the influence of the interaction between metabolism and epigenetics during trophectoderm specification and differentiation, but mostly I just like to culture cells.
Anne Wenzel: Bioinformatician – Steering clear from the wet lab at all times, I try to make sense of the data that gets generated by my teammates. I integrate various omics data or assisting my lab mates in their data analyses.
Jan Żylicz: PI – I take care of people, grants, ethics and papers; also, I tend to occupy people’s benches when I want to show that he can still do experiments.
Favourite technique, and why?
Jan Żylicz: Definitely ChIP-seq, beautiful peaks give me great satisfaction and I can explore them for days. This process typically serves as the initial step in formulating a detailed hypothesis, which can later be tested functionally.
Apart from your own research, what are you most excited about in developmental and stem cell biology?
Jan Żylicz: The role of mechanics in every aspect of a cell’s functioning never ceases to amaze me! I am excited when previously unanticipated perspectives of developmental biology emerge. Our field is rapidly progressing in this direction. Indeed, last years have demonstrated clear couplings between cell and tissue mechanics with transcription, chromatin, and even metabolism. Despite these exciting discoveries, the molecular understanding of these inter-modal couplings remains poorly understood and lacks integration into in silico modeling. I can’t wait for this to actually happen!
How do you approach managing your group and all the different tasks required in your job?
Jan Żylicz: I consider my primary responsibility to be taking care of the entire team. I provide support in various aspects, such as encouraging them to generate ideas, assisting in troubleshooting, aiding with writing tasks, and helping them plan for their future steps. However, in practice, it can become challenging to manage multiple tasks simultaneously. Given my inherent disorganization, I rely on many tools to keep things organized and on track.
What is the best thing about where you work?
Arnau Casoliba Melich: The people and specially labmates are very supportive. We all go through similar experiences and knowing people are there for you is very reassuring.
Antar Drews: Having labmates that help me with (and sometimes prevent me from) consuming concerning amounts of gummy bears in the office.
Eleni Kafkia: I really appreciate the supportive and collaborative atmosphere within and across the labs at the institute.
Viktoria Lavro: The environment is very supportive, not just within my group, but also across other research labs. On top of that, I really appreciate our central location in the city, in a lively area of beautiful Copenhagen.
David Pladevall Morera: The collaborative environment across labs in our institute and the always supportive colleagues.
Nikolaos Stamidis: The individuals from the institute are the ones who create an environment that you truly want to work in. Additionally, I would like to highlight the institute’s incredible facilities and its central location in the heart of Copenhagen, which places it at the center of Denmark’s scientific community.
Karlien van Nerum: The international treats when our colleagues return from holidays.
Anne Wenzel: We have a highly interdisciplinary and international environment with ample opportunities for exchange in scientific and social settings, such as the ChatBPC (BioinformaticsPeerCommunity) meetings and “Friday Hygge”.
Jan Żylicz: Our institute has a close-knit atmosphere, where you get to know everyone personally. Additionally, due to our shared use of similar tools and approaches, we frequently collaborate with labs located right next door.
What’s there to do outside of the lab?
Sandra Bages Arnal: During summer there is plenty of live music around the city, some for free, and in general there is a very nice atmosphere everywhere.
Arnau Casoliba Melich: You have plenty to do in Copenhagen, from cute cafés to great parks, there is always a new thing to do. I specially like the climbing gyms around the city.
Antar Drews: Although Copenhagen is not famous for having great weather, there are plenty of cozy cafés and bars to hide from the rain! Also, people are very sporty and there is a large running community here, which I personally find very motivating.
Eleni Kafkia: The concentration and diversity of museums, galleries, events, and activities make Copenhagen a city with incredibly rich cultural offerings. This, in combination with Copenhagen’s international atmosphere that melds local traditions with foreign influences, contributes to its distinct cultural uniqueness.
Viktoria Lavro: When the weather is good, the city truly comes alive as everyone takes the opportunity to enjoy being outdoors and there are endless events to check out. But you can also always find something fun to do on rainy days, I particularly enjoy attending concerts and playing board games in cafés.
David Pladevall Morera: I love Copenhagen in general and how international the city is. Particularly, I enjoy trying the many different restaurants that the city offers. Although it is a small city, as a capital, you can find great cultural and sport events all year around.
Nikolaos Stamidis: I truly believe that Copenhagen is one of the best cities to live in. The quality of life is very high. Despite the Scandinavian weather, there are many parks around the city where people can be seen exercising throughout the entire year. On top of that, there are always events to attend, and people are always up for going out for a beer.
Karlien van Nerum: As a capital city, Copenhagen is very vibrant and international. You can always find something unique to do and go on little adventures.
Anne Wenzel: Copenhagen is a very livable city. Despite its small size, which means that one can easily get everywhere by bike, it’s still the capital and offers all kinds of entertainment, lots of concerts etc.
Jan Żylicz: The food scene in Copenhagen is truly phenomenal! From street and comfort food to extravagant new Scandinavian cuisine we are spoiled for choice.
Browse through other ‘Lab meeting’ posts featuring developmental and stem cell biology labs around the world.
Doing great science depends on teamwork, whether this is within the lab or in collaboration with other labs. However, sometimes the resources that support our work can be overlooked. Our ‘Featured resource’ series aims to shine a light on these unsung heroes of the science world. In this interview, we spoke to the team behind AxoBase, a new platform providing a one-stop web resource for the axolotl research community.
Homepage of AxoBase
Could each of you briefly introduce yourself?
Prayag: My name is Prayag Murawala. I am an assistant professor at MDI Biological Laboratory. I started my lab three years ago. Before that, I did my postdoc with Elly Tanaka at IMP Vienna. I’ve been working with axolotl for the last 13 years.
Jessica: I’m Jessica Whited. I’m at the Department of stem cell and regenerative biology at Harvard, in Cambridge, Massachusetts. I’ve been working on axolotl models for 17 years.
James: My name is James Godwin, and I’m an assistant professor at MDIBL. I’ve been working with axolotl since 2006.
Joel: My name is Joel Graber. I am the Director of Computational Biology and senior staff scientist at MDI Biological Laboratory. I’m a computational biologist. I’m originally a physicist and computer scientist by training, but I’ve been doing biology since 1996. My job is to manage the computational end of AxoBase, bringing axolotl-related resources together and making them available.
Why and how was AxoBase set up?
Prayag: The Axolotl genome was assembled in two different laboratories several years ago — the Elly Tanaka laboratory at IMP Vienna, and Randal Voss and Jeramiah Smith at the University of Kentucky. Around the same time, there was a salamander meeting initiated by the community. From that meeting, a white paper was published, co-authored by James Monaghan (Department of Biology, Northeastern University), Crystal D. Rogers (School of Veterinary Medicine, University of California-Davis), Jeramiah Smith, Randal Voss, and Jessica Whited.
One of the things listed in the white paper is that we want to have a common platform. This has been discussed in the community for a while, but I think the lack of initiative was the major hurdle. At that time, and even today, there are many different websites, including the Axolotl-omics website, which I beta-tested when I was still in the Tanaka lab. After I took up the position at MDIBL, I was in contact with James Godwin and Joel Graber because they are also faculty here. James was trying to combine the list of antibodies that work with axolotl. I told James and Joel that I would really like to build a resource for axolotl research. We reached out to Jessica as well because of her experience with the axolotl transcriptome assembly. That was how this entire team was formed.
Jessica: I previously trained in flies, so I was very used to having all the genomic resources, mutant and reporter lines easily accessible for researchers. I’ve seen a massive improvement over what existed when I first started in axolotl research, however, there’s still a lot of room for improvement. One of the huge issues is the usability of the existing data. When Prayag, James and Joel reached out about joining forces, I thought that was a really great idea, because it’s really important that the field coalesces to create these kinds of resources. It’s great that we have a cross institution initiative to make this happen. I’m happy to be part of it.
James: I have a similar story. I’ve also worked with mice and it’s just ridiculously easy to do anything genomic as the resources are very vast. But in axolotl, we’re still so far behind and the resources are fractured. I’ve been working with axolotl since 2006, when there weren’t a lot of bioinformatics tools available. You would email someone in the stock center in Kentucky and ask them to look up if they’ve got any genomic data that they can share on your gene of interest. The axolotl genome was published a few years ago, but for an end user, things haven’t moved much in that time. I want the axolotl model to grow, but without those genomic resources in place, we’re not going to attract people into the field.
What is AxoBase?
Prayag: At the moment, we only have links to the Genome Browser and all the resources that are hosted on different websites. We also have an antibody list that James had compiled. The third page lists all the transgenic lines that are published in the field. And then we have a list of labs that are working with axolotl and salamanders in general. The last page is about how we want to develop this, and what are the different areas we want to reach out to. We intend to form committees with the help of the whole community to move it forward.
Joel: AxoBase is still very preliminary. Right now, it’s a community supported information portal for axolotl research. We’re making sure the labs know of each other, that they know of upcoming meetings and things of that nature. It is not yet a genome portal nor the knowledge base that we want it to be.
How can the community help and contribute to AxoBase?
Joel: We’re putting together a proposal, and we need members from the community to help build an anatomical ontology, maintain, and update the gene nomenclature. All of this has to be done in congruence with the external world.
Prayag: We want to integrate all the existing information in the field, including antibodies, probes for HCR in situ hybridization and guide RNAs. But ultimately, no matter how much computation power you use, the annotations are never perfect. The ultimate good quality of annotation comes from the users — the users have to verify that a gene really exists. In axolotl, there are a lot of duplicated pseudogenes. This will require a huge community effort. We require everybody’s participation, whether somebody developed a transgenic animal, used an antibody that is working, assembled the genome or transcriptome, or developed a time course analysis. Eventually, we want to plug this all into AxoBase, so that information we have generated is not lost and can be found easily, not only by existing axolotl researchers, but also for the next generation of scientists wanting to get into the field.
Jessica: One problem, at least in our lab, is the usability of the data from published big datasets. If you don’t have an in-house computational biologist who can help, then it’s really hard. I think we should also be aiming to have a place on AxoBase where the big datasets are hosted in a usable form.
Joel: That’s exactly whatXenbase and many other resources are doing. For AxoBase to really be a state-of-the-art modern resource, it has to be tied into, for example, the Alliance of Genome Resources, which links together the model organisms. The other model organism communities have had a great head start (they do have this slight advantage in that their genomes are much smaller). We are in contact with these organizations, and with the NIH, which has comparative genome resources. We want to talk with Ensembl as well.
All: We are all about aggregation, integration and connection to other organisms. The great challenge with axolotl is it breaks tools because the sequence is so large. We want to make sure that the resources available are linked to the database and connected with known orthologs in other genomes. If we want to apply what we learn in axolotl to other organisms, especially for human health, you have to make sure that the nomenclature and the representations are aligned with each other. Since we are still very much at the formative stages, we want to make sure we don’t waste effort and build AxoBase in ways that are going to have to be reengineered later on to match up with the external model organism community.
Apart from the four of you, are there any other people who are involved in this resource?
Jessica: The Broad Institute is also involved in this. My main computational collaborator for many years has been Dr. Brian Haas at the Broad Institute here in Cambridge. He developed the Trinity program for reconstructing de novo transcriptomes, he has a longstanding interest in axolotl biology, and his expertise has been critical in many of our projects. Joel also knows Brian from the olden days, so he’s going to be working with Joel on AxoBase.
Prayag: Elly Tanaka, Randal Voss and Jeramiah Smith are very crucial in making this happen. We are still figuring out what role they will play in AxoBase. But all of them have been extremely crucial, including Brian Haas, for the success of this portal. I would also like to mention Peter Vize and Aaron Zorn at XenBase, who are very supportive of our effort. The long-term idea is to take a XenBase clone and populate it with the Axolotl datasets.
Joel: XenBasehas a model for doing this already. They’ve successfully migrated EchinoBase from a XenBase clone. It makes sense for us to make use of this, in terms of computational efficiency and saving time and money.
All: A lot of people put their money and effort into making progress in the axolotl field. What we are trying to do at AxoBase is not to reinvent the wheel. We want to take everybody along on this journey and give everybody due credit. The main thing we have been doing is to talk with everyone who has been crucial in moving the field forward, whether in axolotl, XenBase or AGR (Alliance of Genome Resources). There is a lot of behind-the-scenes conversation going on with many different parties involved, getting them all on board so that eventually we can have a proper knowledge base like most other established organisms have.
Even though AxoBase is still in its early stages, are there any features or ‘hidden gems’ that you want to highlight?
Prayag: One of the biggest gems is the antibody collection that James has gathered. If you are working with axolotl, one of the biggest challenges is that most commercially-available antibodies do not work. That’s why on AxoBase we have a list of antibodies that we know work.
James: The antibody collection is community contributed. People can put forward their rockstar antibodies that they are really sure of. They can submit pictures and evidence showing how an antibody works well for a particular application. Hopefully we’ll get more submissions as time goes on.
Where does the funding come from?
Joel: Prayag, James and I are funded through the NIGMS (National Institute of General Medical Sciences), and Jessica’s work is funded by NICHD (National Institute of Child Health and Human Development) and NSF. So you can say the work we’re doing for AxoBase is funded indirectly by the NIH, NICHD and NSF. We are actively seeking other funding, primarily from the NIH, but the NSF is not out of the question.
Jessica: This is part of the issue. We are all putting in the effort, and at some point, we have to account for it financially. We can’t just scrounge around forever and expect that we’re going to get this awesome resource when people need to be supported.
What are the plans for AxoBase in the next few months?
Jessica: One feature we want to have on AxoBase is guide RNA prediction for your gene of interest.
Joel: Another feature that is coming soon isHCR (Hybridization chain reaction) probes. We have predictions for all of the known transcripts, so we just need to build the interface that will allow them to be searched and visualized in a nice way. I’d like to see the HCR probes and the guide RNA prediction available on AxoBase within the next year or so.
James: HCR is the current standard for in situ hybridization, equivalent to RNA scope used in many mammalian systems. You can multiplex, and it works really well in axolotl to work out where the gene is expressed in your tissue of interest. It’s become an important tool to validate single cell RNA sequencing data.
Prayag: The other thing is, being a non-standard model organism, we do not have a lot of antibodies. So in situ hybridization techniques are much easier because we know the transcript sequence, and can design the probe against it. This technology is going to be very useful for axolotl researchers.
Any final words for the Node readers?
AxoBase is an enabling resource. It enables biology to get done. We’re not resequencing anything —we’re putting everything together for improved usability. Our hope is that, not just axolotl people, but even non-axolotl people can easily access all this information as per their need. This will eventually allow more people to use axolotl as a model organism and grow the entire axolotl community.
As readers of the Node’s monthly preprint round-up will know, it can be hard to keep up with the ever-growing number of preprints. That’s one of the reasons why Development started publishing ‘In preprints‘ articles – short perspectives that highlight one or a handful of notable preprints that have recently been posted. These pieces serve to point our readers towards relevant preprints that might otherwise escape their attention, as well as to discuss some of the latest advances in the field. In recent months, we’ve highlighted papers on interface surveillance in developing epithelia, the generation of six-legged mice and the flurry of preprints reporting human stem cell-derived embryo models – some of which made the news headlines, but others you may have missed.
As preprint enthusiasts, we’re keen to expand this section of the journal, so if you’ve recently read a preprint you think is important for your field and you’d like to spread the word about it, please do get in touch with us. We see writing these pieces as an opportunity to strengthen networks, and so are particularly keen to receive proposals from a partnership of authors who don’t directly work together (for example, a senior investigator teaming up with a junior PI). Your proposal should include: the title and DOI of the preprint(s) you want to cover, a brief explanation for why you think it is/they are noteworthy, and a proposed author list. We may not be able to consider all proposals, but we hope that – through this initiative – we can help to highlight and curate the preprint literature.
For early career researchers interested in writing (less formally) about the preprint literature, we’d encourage you to consider joining the preLights team – more information on how to apply can be found on this page.
This summer, I had the opportunity to work at the Francis Crick Institute. Because my early university experience was disrupted by COVID, receiving an opportunity to get some real research and lab experience was something I could not pass up. The Crick has a very collaborative and diverse work environment, along with a range of weekly interest groups and seminars; therefore, coming to the Crick was an easy decision to make. I worked in the group of Robin Lovell-Badge and I was supervised and mentored by Richard Clayton who is a postdoc in the lab.
Oligodendrocyte precursor cells and the median eminence of the hypothalamus
Robin’s lab focuses on the genetics of development and stem cells; Richard’s work in the lab is to investigate the role of oligodendrocyte lineage cells in health and disease. Oligodendrocyte precursor cells (OPCs) are glial cells of the central nervous system that have some stem cell-like properties. OPCs eventually differentiate into myelinating oligodendrocytes, but also into other cell types to a lesser extent (Akay, Effenberger and Tsai, 2021). While I was at the Crick, I got involved in studying the OPCs of the median eminence (ME), which is a small section of the hypothalamus. The ME contains nerve endings of neurons that control the secretion of pituitary hormones and thus, the function of the hypothalamic-pituitary axes and neuroendocrine system is dependent on the ME (Clayton, Lovell-Badge and Galichet, 2022). Proper functioning of the neuroendocrine system is vital for healthy bodily functions.
Figure 1: Confocal projection of a dissected median eminence (left) and the same data as a 3D render(right). The green cells are microglia, in red are OPCs, and the white channel is nuclei.
Figure 1 shows one of the MEs I got to dissect from a mouse brain. The images show that the ME is like a little boat or cup shape which sits right at the base of the hypothalamus. Where the pituitary gland attaches to the pituitary stalk can be seen in the image on the left. This dissection was extremely difficult as the ME is tiny, and could only be seen due to a few key blood vessels that can be seen under a stereo microscope. In one of the genetically modified mice used in the lab, the OPCs are marked with red fluorescence (Galichet, Clayton and Lovell-Badge, 2021); the image shows a high density of them at the bottom of the ‘boat’ that is the ME (Figure 1).
OPCs may be involved in regulation of the neuroendocrine system from within the ME, for example, one study found that OPCs in this region are important for body weight control and leptin sensing (Djogo et al., 2016). Another study from within my lab has found deficits in proliferation and differentiation of OPCs in the ME in mouse models that have hypopituitarism – specifically, mice that are mutant for certain Sox genes (Galichet, Rizzoti and Lovell-Badge, 2023). Cells which were previously thought to simply function as precursors to oligodendrocytes may actually play a much bigger role. An open question is whether OPCs in this part of the brain could control growth by regulating growth hormone (GH) secretion.
The hypothalamus, growth hormone, and side-effects of radiotherapy
Post-natal growth is driven by the hypothalamic-pituitary-somatotropic axis. Figure 2 shows how GH is released from the pituitary. The somatotropic axis involves the release of growth hormone releasing hormone (GHRH) from the arcuate nucleus of the hypothalamus. This then travels down through the ME into the anterior pituitary. Here, somatotrophs release GH into the blood stream for a variety of functions, including the release of insulin-like growth factor-1 (IGF-1), which is vital for post-natal growth.
Figure 2: The hypothalamic-pituitary-somatotropic axis. Created with BioRender.com
Changes in GH levels can result in hypopituitarism, or growth hormone deficiency (GHD), leading to a range of diseases and symptoms, including a lack of normal growth. Approximately 50% of children that undergo cranial radiotherapy will develop a neuroendocrine disorder like GHD (Merchant et al., 2011). Since radiotherapy works by targeting rapidly dividing cells, and because OPCs are the most proliferative cell type in the brain, hypopituitarism has been linked with a decrease in OPC differentiation and survival. Therefore, one of the aims of my project was to characterize the changes of OPC numbers and hormone levels in mouse models of GHD.
Mouse model of GHD caused by radiation
One of these models involves the use of X-ray radiation to the brain to achieve the OPC ablation. However, radio-ablation of OPCs is inherently hard to study, as they are very re-generative and proliferative. Once ablated, new OPCs return rapidly. GHD is also difficult to measure due to the pulsatile nature of GH secretion (levels in the blood are known to fluctuate over time).
Nonetheless, we hypothesized that radiation would ablate the OPCs and result in hypopituitarism. Importantly, the chances of developing GHD increase if patients are younger at the time of the radiotherapy treatment (Pollock and Cohen, 2021). Hence, part of the project also aims to establish whether irradiation affects GH levels and OPCs differently at different ages. I counted the numbers of OPCs and measured the amount of GH and myelin levels in mice that were irradiated at a young age, and compared this to mice that were irradiated as adults.
Figure 3: This graph shows the levels of growth hormone (GH) between sham control and irradiated male mice. The asterisk represents statistical significance with a p-value <0.05.
Figure 3 illustrates results from the ELISA I carried out on the younger mouse cohort; it shows that there is a significant decrease in GH levels of irradiated male mice. This indicates to us that these mice are a potential model for GHD.
Correlating with OPC numbers: Immunostaining and imaging
Next, I carried out a range of immuno-stains for certain cellular proteins on coronal mouse brain sections to correlate the changes in GH with changes in OPCs in the brain. These proteins include myelin basic protein (Mbp), which stains for myelin; Olig2, which stains oligodendrocytes and their precursor cells; Pdgfrα, which stains OPCs, and DAPI, which stains DNA and therefore helps visualize cell nuclei.
Prior to staining, the mice would be culled and I would dissect the brain. I then processed the brains by sectioning them into smaller sections. I’d either cut it with the vibratome or the cryostat. The vibratome slices by pushing its blade across the sample at high vibrational frequencies; this was for sections around 50um thick. The cryostat was for sections around 10um thick, and used a fine blade kept at around -20C. Both were difficult to get used to at first, but I got better over the 9 weeks. The process was very exciting and I really enjoyed being able to personally visualise the anatomy.
Once sliced, I’d carry out the immuno-stains for different marker proteins and then mount the slides for imaging. I visualized the slides under the confocal microscope.
Figure 4: This shows two coronal sections of mouse brains, focused on the median eminence and the ventral hypothalamus. The left shows the control sham, and the right the irradiated. The sections are stained for Pdgfra+ in white, which is a marker of OPCs and also the meninges.
Figure 4 indicates that there is a clear reduction in OPCs in the ME of adult irradiated mouse brains. It also appears that there may be less within the arcuate nucleus of the hypothalamus, as well as the cortex. A surprising find was that within irradiated mice, there are parts of the brain that are less affected by the radiation – mainly the thalamus. This confirmed a previous observation of a difference in sensitivity of different regions of the brain to radiation (Irvine and Blakemore, 2007).
Perhaps the OPCs in the cortex and the ME are simply much more proliferative than those in the thalamus and hypothalamus. Another idea is that the OPCs in differing brain regions have different origins, functions, and properties that may make them more resistant to irradiation. This was quite an exciting idea, because if some OPCs are intrinsically resistant to radiation, we could use their properties to design a therapy that could subsequently make the OPCs of the ME resistant to radiation. Perhaps this could aid us with respect to the radiotherapy-linked GHD problem.
A genetic mouse model of growth deficiency
Next, I wanted to understand more about how loss of OPCs could lead to GHD. One idea is that OPCs are needed to support development and maintenance of GHRH-secreting neurons. To investigate, I used another mouse model where mice have mutant copies of a Sox gene. These mice have a growth deficit phenotype that indicates they could have GHD. The mice I used also had a fluorescent marker present in GHRH-secreting neurons, which meant I could count the overall number of neurons in the brains of these animals.
Figure 5: This shows the arcuate hypothalamus under the confocal microscope (left) stained for DAPI (blue) and GHRH neurons (green). The graph on the right compares the average GHRH neuron counts of the arcuate hypothalamus between the Sox mutant and wildtype mice.
The preliminary results suggest there is no difference in the number of GHRH neurons of Sox mutant vs wildtype mice (Figure 5). This suggests that the lack of GH is not due to a relative reduction in neurons in this model. Therefore, it may imply that while the number of neurons is unchanged, the Sox mutation affects the OPCs in a way that leads to a decrease in the amount of GHRH released. We could investigate this further by staining for recently active GHRH-secreting neurons to investigate their activity, both in Sox mutants but also in irradiated mice. Furthermore, we could carry out an ELISA or radioimmunoassay for GHRH to directly investigate the hormone levels.
Overall, my summer at the Crick was an unforgettable experience; I wish I could do it all over again. I learned an incredible amount over the 9 weeks, not just from my lab, but from the many seminars and talks that were available to us, and from all of my fellow summer students. Being in an environment where I was encouraged to always ask questions, and being somewhere where the scientific conversations continued over lunch and coffee, were some of my favourite aspects of my time at the Crick. The lab I was in had incredibly passionate and smart people in it, who made sure weekly lab meetings and coffee breaks were never boring. I thoroughly enjoyed being around people who share the same interests as me and who always want to learn.
I also gained valuable experience in conducting research and gained new skills of wet- and dry-lab techniques. I am a lot more confident and excited for my final year of undergraduate study, and I feel much more prepared – mentally and physically – for my dissertation project. Lastly, this experience has also opened the new avenue of pursuing a PhD which, until now, I had not properly considered.
Finally, I would like to thank the Francis Crick Institute for hosting me and the Medical Research Foundation Rosa Beddington Fund for supporting my project. I would also like to say thank you to everyone I met at the Crick. I had such a great experience, and I fully recommend that everyone should do a summer studentship!
Akay, L.A., Effenberger, A.H. and Tsai, L.-H. (2021) ‘Cell of all trades: oligodendrocyte precursor cells in synaptic, vascular, and immune function’, Genes & Development, 35(3–4), pp. 180–198. Available at: https://doi.org/10.1101/gad.344218.120.
Clayton, R.W., Lovell-Badge, R. and Galichet, C. (2022) ‘The Properties and Functions of Glial Cell Types of the Hypothalamic Median Eminence’, Frontiers in Endocrinology, 13, p. 953995. Available at: https://doi.org/10.3389/fendo.2022.953995.
Djogo, T. et al. (2016) ‘Adult NG2-Glia Are Required for Median Eminence-Mediated Leptin Sensing and Body Weight Control’, Cell Metabolism, 23(5), pp. 797–810. Available at: https://doi.org/10.1016/j.cmet.2016.04.013.
Galichet, C., Clayton, R.W. and Lovell-Badge, R. (2021) ‘Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease’, Frontiers in Cellular Neuroscience, 15, p. 673132. Available at: https://doi.org/10.3389/fncel.2021.673132.
Galichet, C., Rizzoti, K. and Lovell-Badge, R. (2023) ‘Sox3-null hypopituitarism depends on median eminence NG2-glia and is influenced by aspirin and gut microbiota’. bioRxiv, p. 2023.07.26.550616. Available at: https://doi.org/10.1101/2023.07.26.550616.
Irvine, K.-A. and Blakemore, W.F. (2007) ‘A different regional response by mouse oligodendrocyte progenitor cells (OPCs) to high-dose X-irradiation has consequences for repopulating OPC-depleted normal tissue’, European Journal of Neuroscience, 25(2), pp. 417–424. Available at: https://doi.org/10.1111/j.1460-9568.2007.05313.x.
Merchant, T.E. et al. (2011) ‘Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors’, Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 29(36), pp. 4776–4780. Available at: https://doi.org/10.1200/JCO.2011.37.9453.
Pollock, N.I. and Cohen, L.E. (2021) ‘Growth Hormone Deficiency and Treatment in Childhood Cancer Survivors’, Frontiers in Endocrinology, 12, p. 745932. Available at: https://doi.org/10.3389/fendo.2021.745932.
Our first webinar in October was chaired by Development Editor Debby Silver (Duke University) and featured three early-career researchers studying neurodevelopment and regeneration. Below are the recordings of the talks.
Baptiste Libé-Philippot (VIB-KU Leuven Center for Brain & Disease Research)
In June of this year, five secondary school teachers who teach BTEC and A levels students from Wales and Oxfordshire spent a week with us at the Department of Physiology Anatomy and Genetics (DPAG) and the Institute for Developmental and Regenerative Medicine (IDRM) at the University of Oxford. Our aim was to support and promote STEM subjects among students by providing their teacher the opportunity of a residency in a modern research setting, where they could experience how research is conducted on a day-to-day basis, network with researchers and generate their own experimental results to enrich their teaching.
PhD Student, Esra, is showing zebrafish embryo to participating teachers (IDRM)
The program was fully funded by Jesus College and Trinity College, Oxford, who sponsored transportation, accommodation and meals. We also received funds from DPAG for substitute teaching cover for the schools while their teachers were with us in the lab, which the participating teachers said was absolutely essential in enabling the schools to let them join the week long residency. We had a great deal of interest in the scheme and more teachers than we could accommodate applied to take part.
We asked the teachers why they chose to spend a week away from home and work and here is what Clare, a secondary school teacher from Oxfordshire said:
“I realised that although I had taught science for 20 years, I knew nothing about a career in Scientific research or as a science lab technician in research. I had many A level students interested in this area who would ask my advice, both gifted students who wanted to do a PhD and work as a research scientist, and students who were excellent practically and wanted to work in some capacity within science.
I felt that I needed to know more in order to support and advise them. I also wanted to develop my own practical techniques, having studied a degree that was almost entirely theoretical, with almost no lab experience. In addition, my school had asked me to help giving students mock interviews for Biology, and I felt I needed to know more about the Oxbridge interview process.”
At hosting institutes, the teachers spent their times with researchers in their labs. A daily work plan (with associated risk assessments) was prepared beforehand and shared with the teachers, researchers who worked with the teachers and local safety officer.
At DPAG, two teachers shadowed researchers one-on-one, following their research. The teachers and their host researchers in this group had several productive discussions on details of the research: “The experience of having been with a [resident teacher] was a win-win exercise. On my part, knowing how a teacher organises their classes, understanding the way that they see things, and how they are always thinking about how to make things comprehensible for others, I would say that I was sharing the bench with an expert in public engagement.”
“From [the teacher’s] side, she was fascinated by how the theory is put into practice in a research project, from the experimental design, and going through the methods, to how the results are analysed and discussed how they are in line with the research project hypothesis, I remember she said: ‘I could go back now to my student and talk about this experience for weeks and weeks” said Mayra, one of the researchers.
At the IDRM, three teachers participated in hands on experiments and attended research talks. Eight host researchers at the IDRM formed a group to work with the three teachers, and set up typical experiments to introduce them to research topics. Teachers formed a group to work on an experiment together as well as one-on-one with a host researcher. Some of the activities included:
Whole mount Hybridization Chain Reaction on E9.5 mouse embryos
Harvest and culture of pre-implantation mouse embryos and cave fish embryos
Imaging injured adult fish hearts
Basic tissue culture technique and organoid differentiation
Genotype PCR, confocal imaging, etc
The teachers also enjoyed learning about available public engagement/outreach resources, listened to talks taking place at the IDRM, and met with staff with different training backgrounds. The teachers felt it was particularly useful for them to meet research staff with a non-traditional entry into a career in research, as there are students who love science and experiments who might not think academia is for them, and they can encourage these students to aspire to a career in research.
The experience was tremendously fulfilling for teachers and researchers alike. Work with the teachers provided the researchers a valuable opportunity to think about the societal context and impact of their research, how to talk about the relevance of their research, and of course, gave them the opportunity to talk about the science that excites us all.
If anyone is interested in doing something similar and would like tips, please don’t hesitate to get in touch with us!
Participating labs and their locations:
DPAG – Kavli Institute for Nanoscience Discovery: Carlyle and Lakhal-Littleton groups
DPAG – Institute of Developmental and Regenerative Medicine: Mommersteeg, Riley, Srinivas, and Stone groups
Many thanks to the participating teachers, Jesus and Trinity College Access Officers, DPAG EDI officer, and researchers who donated their expertise and time.
Every time there’s a frost, I go out and look at all these plants and think, I wonder what’s been induced. I think by looking at the plant, it tells you the questions to go and pursue… There is so much to understand about how plants change in response to the environment.
Professor Dame Caroline Dean, John Innes Centre, Norwich
In the latest episode of the Genetics Unzipped podcast, we’re exploring how plants adapt to a changing environment, and how we might be able to give them a helping hand so that we can keep feeding the world sustainably in the future.
If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip
Our second webinar in October will be chaired by Development’s Associate Editor Irene Miguel-Aliaga (Imperial College London) and features three early-career researchers studying metabolism and development, which coincides with the completion of Development’s Special Issue: Metabolic and Nutritional Control of Development and Regeneration. The webinar will be held using Zoom with a Q&A session after each talk.
Wednesday 25 October 2023 – 15:00 BST
Maria Fernanda (Nanda) Forni (Yale University) ‘Metabolic crosstalk during regeneration and aging impacts tissue homeostasis in the skin’
Hidenobu Miyazawa (EMBL Heidelberg) ‘Metabolic signaling as a regulator of developmental timing’
Siamak Redhai (DKFZ) ‘Identification of Chronophage as a novel transcription factor involved in Notch signaling during intestinal stem cell differentiation’
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