On Thursday 23 February I visited the Crick Institute in London to see their new exhibition, Cut + Paste, and to meet the organisers. Cut + Paste is an interactive exhibition that invites attendees to learn about applications of genome editing currently being implemented or those that are being investigated as potential solutions to environmental, food supply, or medical problems facing 21st century humanity. Equally importantly, the exhibition aims to engage visitors, make them think about potential risks in the technology, and ask them for their own opinions.
The exhibition was organised by creative consultancy ‘The Liminal Space’ in collaboration with the Crick’s public engagement team, with Professor Robin Lovell-Badge and Dr Güneş Taylor, researchers at the Institute, serving as scientific advisors.
Image from the Francis Crick Institute
The exhibition is small, engaging and informative, and is designed to appeal to as wide an audience as possible, in terms of age but also familiarity with the topic. After giving visitors a brief tour of the DNA and its information storage unit, the gene, the exhibition introduces gene editing as a method to introduce precise edits to the genome, both large-scale as well as single-‘letter’ edits. The exhibition then gives an overview of the various applications of genome editing that are already in use and those being investigated with the aim of solving some of the world’s pressing problems. Among some of the topics explored by the exhibition are the editing of plant genes to make plants more nutritious; modifying the genes of livestock to make them emit less methane, a greenhouse gas; curing or treating human diseases such as sickle-cell anaemia; or ‘enhancing’ humans with new characteristics, such as making them resistant to HIV infection or curing deafness.
The best thing about the exhibition, in my opinion, is the high degree to which it invites viewers to contribute their opinion. Early on in the exhibition, viewers are asked which traits they’d want to pass on to their children (Science whizz? Sense of humour? Compassion?) and to combine their selection into a ‘gift.’ Later, attendees can read arguments on the potential pros and cons for each of the applications of genome editing and are invited to show how keen they are to see this application come to life by throwing a ping-pong ball into one of five ‘bins.’ Interestingly, but perhaps unsurprisingly, applications directly associated with human genome editing seemed to be more controversial. I had the opportunity to do a bit of my own research on visitors’ attitudes by calculating how popular each application was. At the end of the exhibition, visitors can record their thoughts into a microphone or write their opinion on a note card and hang it up on a ‘web of ideas’ along with others’.
Plant power – should genome editing be used to help resolve global health issues? Climate-friendly cows – should genome editing be used to help solve environmental crises? Sickle cell disease – should genome editing be used to cure inherited diseases? Super humans – should gnome editing enhance our minds and bodies? Malaria research – should genome editing be used on entire species to get rid of infectious disease? New frontiers – should we use heritable human genome editing for challenges that could be solved in other ways? Visitors to the exhibition are not as ready for editing human genomes to have enhanced traits or for addressing challenges that could be otherwise solved.Image from the Francis Crick Institute
I was able to talk to some attendees on the day and ask their opinion. Jaz and Chloe mostly agreed with genome editing for the treatment of diseases and the improvement of human health but disagreed about the risk of gene-edited crops or animals potentially altering the ecosystems they are released into. They both loved the interactive/game-like element of the exhibition. Clearly the exhibition provides a lot of food for thought!
There are aspects [genetic traits] I would want to ensure that wouldn’t be passed on but my worry is it will go too far and cause further divides in society. This would likely not be covered by national health care and allow richer people to advance themselves and widen the wealth gap.Where would you draw the line?Yes! I think we should be embracing gene editing to solve problems like climate change. Our climate is evolving rapidly, I think it makes sense to respond ‘rapidly.’
I also had the opportunity to talk with Dr Taylor about the exhibition in more detail, and their involvement with public engagement in the context of scientific research.
For the Cut + Paste exhibition, could you take us through the process from the initial conception to the final exhibition?
Cut + Paste was first conceptualised before the pandemic. When the Crick was first started in 2017, [genome editing] was put forward as a good subject to cover soon [in the Crick’s exhibition space], because it’s timely and it matters. The idea at the time was to have a small trial exhibition, where we tried different concepts to see how the public responded to different ways in which this information could be presented. Then the pandemic put everything on ice. So as we were coming out of the pandemic, it was decided that we would re-engage the project, and develop it into a full-sized, full-year exhibition.
The important point of the starting phase is to have conversations that capture all the things that you think are important and to have some dialogue about “Which of these many different things should we be talking about as a biomedical research institution?” Importantly, one of the big things that happened in the course of this was [that] it went from just being, “Here is an exhibition just explaining what genome editing is,” to becoming not really an exhibition per se, rather a space to engage with difficult ethical questions stemming from genome editing. So you’ll notice that it’s not really pictures of Cas9 and CRISPR everywhere. It’s deliberately designed to be more about those questions than about the technology in itself.
Absolutely. Ok, so, in that vein, how did you choose which specific genetic modification ‘case studies’ to highlight in the exhibition?
There are six case studies, scenarios, and of them, one is about plants, one is about livestock, one is about pests that carry diseases that affect humans, and the other three are all about humans directly. That’s a reflection of the fact that we’re a biomedical research institute. We don’t actually study plants or even livestock [at the Crick]. But it was important to flag them, because we were keen to get across this idea that anything on Earth that has DNA can now be edited using this technology. The potential ramifications of this technology are all-encompassing, and we really wanted people to understand that.
Also people feel quite differently, and much more strongly, about the human scenarios. So, it also functions to bring people into the right headspace to think about it. It’s one thing to think about a plant: “How does that affect food and food supplies?”, and then thinking about livestock, there’s a bit more ethical concern, “What about their welfare?” There’s a bit of a sliding scale, naturally, in that.
What are you hoping will be the major messages and takeaways of the people who attend the exhibition? Do you plan to track responses to questions in the exhibition to assess what attendees’ opinions are and how they may have changed as a result of attending the exhibition?
Exactly. The key information that we’re hoping to get across is that genome editing is a technology for changing DNA, and there are different contexts under which you can use this technology, but the main thing that we wanted was for people to engage. Often people initially think “I’m not a scientist, I don’t know.” We wanted to overcome that, such that people feel empowered and have a sense of agency about these conversations.
The second thing [we wanted to get across] is, of course, an immediate appreciation for the fact that there is a diversity of opinion on, and value in, each of the scenarios that we present. You’ll notice that the scenario cards [in the exhibition, describing pros and cons of each potential genome editing scenario] deliberately have opposing opinions, and that’s important to remember, in this context especially. It’s to make people comfortable to engage, but also comfortable and aware of the fact that some people disagree.
And then of course the final thing is that we have this ‘make your mark’ section where we invite people to vote and write things down and record their thoughts, and as a research institute we will be keeping record of that, and it will potentially feed into statements we will make in the future regarding genome editing and future policy decisions.
You’ve been involved in science communication for several years. What about it do you find exciting and important? What about science communication would you like both the scientific community and members of the general public interested in science to know?
I think that many scientists still think that it’s pointless, and I obviously disagree with that. I was always raised with this idea of the Victorian scientist who does the experiments and then gives the public lectures, so I thought that was completely normal. It wasn’t until I started the PhD that I realised people are very hierarchical in academia, like “Who are you to go out and talk to the public? You don’t have a Nobel prize, who cares?” But, on principle, we are publicly funded. I felt very seriously that I am funded by the public, it’s charity money that’s giving me my salary to do this, so if the public want to know about something, they have a right to know.
Actually, whether I’m talking to a biochemist, or an engineer, or an electrician, there’s not really that much difference. I would classify [all] as public engagement. You talk to anyone outside your field, it’s basically public engagement, because most people don’t know about the finer nuances of your field. It’s been real training for me in how to communicate clearly. And I didn’t go into it for that, but since realising that that’s a side effect, I’ve encouraged as many people as I can to get comfortable doing that. The true challenge in trying to demonstrate mastery of something is to be able to accurately transmit that information in simple terms. And there is no better context under which to do that than public engagement.
The last thing to say about it is, at least in my experience, academia is extremely hierarchical, and that can corrode one’s self-confidence a lot. For me, science communication has been an antidote to that. A different context under which I can practice remembering that I am an expert, of sorts. That’s more of an amorphous benefit, but I think it’s really important because we don’t get much gratification in our line of work. It’s not often that a big experiment works. But it can be so satisfying to have that moment of being able to say “You didn’t understand what DNA was when we started this conversation, and now you asked me a really smart question, so I know you understand.” And that immediate gratification, at least for me, has been really helpful.
Do you have any short- or longer-term plans for public engagement events on any other topics?
I don’t actively plan them. If I get invited to do something, or if somebody wants my opinion, I will give it. I value ‘engagement’ with a little ‘e,’ if that makes sense. For me, the way to have a tangible impact comes from the personal interactions that you have with people. It’s just engagement with a little ‘e’ rather than with a capital ‘E.’ It’s not in the context of an institution, but those are the moments that for me never stop. Someone says “What do you do?” and you say “I’m a scientist,” and then almost inevitably they say “I didn’t do well at school at science,” or “I’m really bad at maths.” For me that’s an opportunity to engage and say “Yeah, me too, but I just really like it.” And to normalise that conversation about science is really timely. The pandemic, if nothing else, proved that there is a moment right now where people really see that science is important, but maybe don’t know how to engage or still feel very much like science is something that scientists do. [But] the reality is, the scientific method – the ability to observe, hypothesise, and rationally interrogate information – is not something that only scientists do. And for me, that’s the heart of any of these things.
The Cut + Paste exhibition is open to visitors Wed 10:00-20:00 and Thurs-Sat 10:00-16:00 at the Crick Institute until December 2nd 2023.
One of our favourite giveaways here at the Node is our collection of postcards. With our supplies dwindling (they are a crowd-favourite at meetings!), we are planning to reprint the series and we would love to take this opportunity to add some more #devbio favourites to our collection. If you have an image that you think would be make a great addition to the Node postcard collection, submit it to our competition! As well as selecting images for postcards, one lucky winner will be featured on the cover of a ‘Development’ issue in 2023.
There are a few model systems missing or underrepresented in our current collection, so we would especially love to see submissions from featuring in vitro models, plants, teleosts and Xenopus as well as some of the emerging model organisms that will take centre-stage at our ‘Unconventional and Emerging Experimental Organisms in Cell and Developmental Biology‘ Journal Meeting in September.
Thanks to all the researchers that have given us permission to use their images in our current series: we hope you love the set as much as we do!
Deadline: Tuesday 11 April
Competition details:
Email your image to thenode@biologists.com with ‘Postcard competition’ in the subject line.
You can submit up to three images.
In the email, include a description of the image and imaging modality used to acquire the image or software used to reconstruct or analyse it.
There is no theme and no restriction content-wise; it can be a raw, reconstructed, filtered or analysed image of any type of sample.
The postcards are A6 portrait and images may be cropped to fit our design (logo on bottom right).
Development cover guidelines on dimensions require a high-resolution file 23cm width by 24cm height, some cropping might occur in adapting the winning image.
Submitted images should not have already been published elsewhere unless under a CC-BY license (and please let us know if this is the case).
Now that we have a technology that allows us to alter DNA, it means that we can have an impact. We have a choice in the matter of health and bodies of plants, animals, and humans. And so now here is the question: think about anything that you want to in the world about health or about bodies, and now know that we can change that should we wish to. What would you do? What do you think is worth doing? What do you think is not worth doing?
Dr Gunes Taylor
In the latest episode of the Genetics Unzipped podcast, we’re exploring the history and ethics of genome editing, tinkering with the genetics not only of this generation, but potentially generations to come.
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
We are pleased to announce that the Avian Model Systems Meetings are back after COVID. The 11th meeting will take place on 11-14 September 2023 at the University of Portsmouth, UK. The conference will bring together scientists from across the world whose research focuses on birds. The conference website is now open for registration and abstract submission.
Session topics include:
Dynamics of development, morphogenesis, organogenesis
We have lined up exciting keynote speakers. Further speakers will be selected from abstracts, and all attendees will be able to present posters. We will have a plenary discussion with funders and stakeholders on the future of avian models and avian research, and we have set time aside for a PI meeting to discuss the development of resources for the avian research community.
Besides the science, Portsmouth is the attractive waterfront city at the South coast of England, known for its maritime heritage and the Portsmouth Historic Dockyard, with quick links to the Isle of Wight and the South Downs National Park. Portsmouth is also known for its shopping opportunities. Portsmouth can easily be reached via London Heathrow and Gatwick airports and Southampton airport. It also has ferry links with the Channel Islands, France and Spain.
The Organising Committee look forward to welcoming you to Portsmouth!
Hi everyone, my name is Laura Hankins and I’ve recently joined Development as a Reviews Editor. I haven’t moved far, as I initially joined The Company of Biologists back in 2021 as their Science Communications Officer. That role gave me the opportunity to work with lots of different teams within the company and provided me with an insight into how publishing operates behind the scenes. I’m excited to build on this experience as I settle into the Development team.
Before joining The Company of Biologists, I completed a PhD at the University of Oxford via the Wellcome Trust’s four-year DPhil in Chromosome and Developmental Biology. After rotation projects with Paul Riley and Neil Brockdorff, I settled in Jordan Raff’s lab where I worked on centriole biogenesis in early Drosophila embryos. This involved plenty of microscopy! During this time, I was lucky enough to be awarded a place on the 2019 Physiology Course at Woods Hole, MA. This was a fantastic experience that exposed me to even more microscopy and various quirky organisms, as well as allowing me to meet many wonderful scientists from a range of career stages and research backgrounds. This sense of community was something that I really missed when the pandemic struck towards the end of my PhD.
I’m therefore delighted that I get to stay in touch with the scientific community in my new role. I’m looking forward to working with authors to produce front section content for the journal, and to getting to know the community better as I start to attend meetings and workshops. Please feel free to contact me via email or LinkedIn, and hopefully I’ll get the chance to meet some of you in person over the coming months!
Our sister community site preLights is celebrating its 5th birthday! 🎉
To mark the occasion, a festive webinar has been organised that features talks given by preLights alumni who have all made significant contributions to preLights, and have since taken a range of career paths. In these talks, they will tell us how they have managed to identify and navigate the challenges, opportunities, and obstacles they faced as early-career researchers and how these have all led them to where they are today. Also, they will tell us a bit about their current position and future goals and ambitions.
Following a brief presentation by each speaker, there will be a Q&A session.
The webinar is free and open to all, and a link to the recording will be made available to registrants.
In our latest SciArt profile we hear from Robin Cassady-Cain, a professional artist based in Canada. Robin’s scientific background is in immunology and many of her artworks are inspired by the human immune system. As well as creating stunning jewellery, Robin uses her artwork as educational tools.
Where are you originally from and what do you work on now?
I was born in Barrie, Ontario, but mostly grew up in Toronto. I did my undergrad in Biochemistry at University of Waterloo, then a Masters in Immunology, and my PhD in Immunology at University of Cambridge. My last research post was at the Roslin Institute, University of Edinburgh, working with Professor Mark Stevens. I was a core-funded Research Fellow, so I worked on large animal models of bacterial enteric infection (the big 3-Campylobacter, Salmonella and various pathogenic E. coli) part of the time, and part of the time directing my own research looking at the molecular mechanisms, biophysical and structural characteristics of a bacterial toxin homologue, Lymphostatin, known to block lymphocyte activation in vitro/ex vivo. In 2018, I moved back to Canada, giving up my research career to become a professional artist.
Yes! The exact time that I decided that I wanted to be a scientist is lost to the sands of time, but it was somewhere in middle school, doing all those science fair projects. I had dreams of being a professor, it seemed so glamorous to me (how little I knew!!). The idea of being a scientist really cemented itself in high school, particularly as I had several supportive and influential science teachers. Science held an endless fascination for me, and although I could imagine doing other things, I felt that research was where my mind and heart were leading me.
Tumbling Earrings: sterling silver, garnet and needled felt
And what about art – have you always enjoyed it?
Yes! I’ve enjoyed looking at art and making things since I was very young. My earliest memory is making clothes on my child’s Singer machine for my Barbie dolls (the only thing I thought they were good for!) Over my life I have done photography, wet and needle felting, papier mache sculpture, quilting, collage, Scottish kiltmaking and, of course, jewellery.
What or who are your most important artistic influences?
I love impressionism, and abstract art, but if you want to know about jewellery/metal arts, Wendy Ramshaw, an iconic British goldsmith had a huge influence on how I viewed jewellery and the art of making jewellery. From her early paper jewellery, her stacking rings that come with their own unique tower storage, and her whimsical story-telling pieces, I love the breadth of her work and particularly some of the geometric lines that she used.
Stem cell brooch: sterling silver, needled felt
How do you make your art?
I work primarily out of a shared jewellery workshop in the west end of Toronto called Jewel Envy. Since I’ve switched to primarily working as a professional artist, I have found community there, which is invaluable. I have an ongoing obsession with immunology and cell forms and concepts clearly influence my personal art jewellery, but I do a lot of work with clients to help them realise their own concepts in jewellery form, and more collaborative work, like some of the pieces showcased here. I worked with an old friend and colleague who wanted to have some jewellery created that reflected some of the cell work that they do with stem cells, and myometrial cells. The end result were two sculptural cell forms—one representing the embryonic stem cell ball, complete with felty nuclei, taken from fluorescence microscopy images. The other is modelled after a schematic of myometrial muscle cells, again with felted nuclei. I do a lot of jewellery incorporating felt, patterned textured, and incorporating semi- and precious gemstones, using the traditional methods of metal fabrication and lost wax casting.
Does your art influence your science at all, or are they separate worlds?
My art used to influence my science, in the sense that it provoked me to think more deeply on some topics, and how things connected together. I found it almost a meditative process that would quiet the part of my mind that was always actively thinking about my science, and allowed insights to float to my conscious mind more easily. Conversely, I’ve carried through so many skills and thoughts that I had about my science through to my professional artist practice.
Spillage ring: sterling silver, sea bamboo, seed pearls and enamel
What are you thinking of working on next?
I continue to explore the themes of the immune system in my jewellery, and I can’t see me ever exhausting my ideas there. I love the fact that every major piece that I do is a potential conversation about immunology and/or opportunity for education. I am also embarking on a collaborative series of mixed media art pieces with another artist that is centred around the concept of herd immunity. It’s just at the very early formative stages, but I can’t wait to see where it takes us!
Thanks to Robin and all the other SciArtists we have featured so far.We’re looking for new people to feature in this series – whatever kind of art you do, from sculpture to embroidery to music to drawing, if you want to share it with the community just email thenode@biologists.com (nominations are also welcome!)
Scott Gilbert is Emeritus Professor of Biology at Swarthmore College and the University of Helsinki. He literally wrote the book on developmental biology! With the 13th edition of ‘Developmental Biology’ about to be published, we took the opportunity to find out more about the story behind the textbook, to discuss Scott’s research career and his social and political commentaries in relation to developmental biology.
Let’s start at the beginning, when did you first become interested in biology?
I think that everyone is initially interested in biology; but for some odd reason, most people aren’t able to keep that interest. Most young people love dinosaurs, turtles, and horses, but they leave those interests behind. I was always fascinated by nature. My summer days were spent in the woods and fields of northern Pennsylvania, finding salamanders, frogs, and butterflies. My scientific career peaked when I was 12 years old. I had caught a five-legged frog, and word of this somehow got to Leonard Lyons, the syndicated gossip columnist for the New York Post. So, I was mentioned in his New York Post column, alongside Josephine Baker, Leo Szilard, and Pablo Casals. I don’t expect to ever reach this pinnacle again. I was also fortunate to have met Dr Jean Cook, a Black haematologist at the Albert Einstein College of Medicine, who gave me my first research experience while in high school. He was fascinated by the ways that life could have originated in the early atmosphere of the planet. In trying to repeat the Urey-Miller experiment, I nearly fried myself, trying to splice wires together while they were still plugged into the sparking coil – a learning experience (and I did get to identify aminoacrylonitriles). In addition to teaching me about erythrocyte development and how to do column chromatography, he also taught me to appreciate and enjoy the music of Julian Bream.
You went on to study biology with religion at university, what prompted you to choose that combination?
I always thought I was going to be a biology major, but in college, I also became fascinated by the study of religion. I came to the conclusion that the ecology movement needed an alliance of science and religion, and that the two areas were actually related. I see ‘Wonder’ as the prime experience that the mind has with the world. But wonder has a short half-life and ‘decays’ into curiosity (I wonder) and awe (the wonder of the world.) Curiosity gives rise to science and philosophy; awe gives rise to reverence and the religious attitude. So, science and religion are both the ‘grandchildren’ of wonder. Moreover, science and religion have a vested interest in keeping those sources of wonder alive. I don’t care whether a person goes into the environmental movement to preserve biodiversity, or to be a proper steward of God’s creation. They’re both motivations for preserving natural wonder, which I feel is critical, among other things, for preserving science.
In 2016, I was asked to give a lecture on developmental biology to His Holiness, the Dalai Lama. After my talk, the Dalai Lama said that he enjoyed the talk, but that the questions of interest to him are: How does the reptilian brain become the mammalian brain, and how does the mammalian brain become the human brain? So, we have a religious leader who not only accepts evolution, but who wants to know the evolutionary developmental mechanisms of neocortex formation!
Do you think that it is important for scientists to comment on social and political issues that are related to their work? Have you faced any criticism for your papers and commentary?
As embryologists we have to deal with issues of sexism, racism, and abortion. If we’re working in evo-devo, we’ll come across creationists. Saying nothing about these social issues is itself a political position. If you have expertise in these fields yet don’t combat publicly stated falsehoods, then you’re basically saying that the status quo is acceptable. Most of my social commentary has been against people misusing developmental biology to say that science supports white supremacist or male supremacist arguments. I think it’s because I love developmental biology and I don’t want to see my beloved being smeared! Having a background in history of biology has helped me enormously in addressing these issues. I’ve written about how scientists in the 1800s tried to use human embryology to show that women and Black people were immature, embryonic, forms of the white male. Until very recently, the female was seen as the incomplete development of the male phenotype.
My most recent paper concerns myths that are currently being used in the abortion debate in America. Each of these myths is represented as science, but none of them has much to do with facts from developmental biology. These myths portray fertilisation as ensoulment, and depict the woman as a passive entity. I also show that different groups of biologists claim different embryonic stages to be the start of personhood (admitting that ‘personhood’ is not really a scientific concept), and that the notion that all biologists believe that personhood begins at fertilisation is ideology, not science. Some biologists say it begins at fertilisation when you get your genome. Other biologists say it begins at gastrulation, where you become an individual and can’t form twins or triplets anymore. Other biologists have claimed personhood begins when you get your electroencephalogram (EEG) pattern, because that’s when the anatomical correlates of consciousness and pain perception form (and we’re willing to say death is the loss of that pattern). Still others say personhood begin around when the fetus becomes viable outside the womb. And some people maintain that personhood begins at birth, when the first breath causes pressure differences that change endothelial gene expression and cardiac morphology, preparing the fetus for life outside the mother. I think the public should be made aware of these different possibilities. I haven’t faced criticism for my views, which probably means they are not well enough known.
Can you give us a brief overview of your research career?
I feel like the surfer that caught the perfect wave. I was at Swarthmore College with a background in developmental biology and history of biology, and that allowed me to catch and ride the waves of developmental biology and the evo-devo wave behind it. As I mentioned, I was an undergraduate at Wesleyan University in Connecticut, where I majored in biology and religion. I did research on the attachment of DNA to the nuclear envelope during sea urchin fertilisation in the laboratory of Tony Infante, and it was published in Nature New Biology. Teaching during the summers at an NSF-sponsored Pre-College Science Center run by Michael Somers convinced me that embryology was the field that most excited me. I pursued my PhD at the Johns Hopkins University in the laboratory of Dr Barbara Migeon, who is most famous for her work in X chromosome inactivation. My project concerned extending amniocentesis to look at the genes of human kidney cells, not just fibroblasts. This was before the days of DNA sequencing, and it meant doing enzyme assays in the cold room. I should mention at this point that I probably hold the record at Hopkins (and maybe elsewhere) for the number of sequential thesis advisors: four. While doing my PhD, I was also able to work on an MA in the history of biology under the direction of Donna Haraway. I did my master’s thesis on how the X chromosome was the bridge between Thomas Hunt Morgan’s embryology and his genetics.
For my first postdoc, I went to the University of Wisconsin to work with Masayasu Nomura, because I thought that E. coli ribosomes would be the best model for looking at the co-transcription of eukaryotic genes. I thought I could prove the Britten-Davidson model using E. coli ribosomes. We published some of the first gene sequences using the Maxam–Gilbert technique with restriction enzymes, polymerases and gel apparatus that we had isolated and made ourselves. Within a few months I had disproven my thesis, but we got some beautiful sequences of the regulatory region for RNA operons! I did a second two-year postdoc in developmental immunology with Robert Auerbach, while my wife was doing her residency in obstetrics and gynaecology. Here, we made monoclonal antibodies against poliovirus, and we discovered the mechanism by which antibodies neutralise the virus.
Moving on to the next step, I wanted a career where I could help raise children, have friends, and do other things besides science. But at the same time, I wanted a life that was saturated with science and research. I found this at Swarthmore College, a liberal art college in Pennsylvania. It had one of the best undergraduate biology departments in the country, and there were some phenomenal students coming into Swarthmore. My first paper from Swarthmore came after I heard a lecture on auxin transport given by our plant physiologist, Mark Jacobs. He had an assay for this transport, but he had no way to identify the proteins involved in transferring the hormone from one cell to another. I suggested using monoclonal antibodies (which I knew how to prepare). So, Mark and I published the first paper (in Science) using monoclonal antibodies to study plant development, identifying the location of the auxin transport proteins. I was able to get NSF grants because I was teaching undergraduate students how to do developmental biology. Originally, I continued my work on kidney development, and in 1990, I had the opportunity of spending a sabbatical leave in Finland with Lauri Saxén. Here, I worked on cell-cell communication and branching morphogenesis in mouse kidneys. I thoroughly enjoyed this time in Finland, and I brought back an interest in studying branched organ morphogenesis. Working with Judy Cebra-Thomas, we delineated paracrine factor involvement in the branching of amniote kidneys and lungs. Then I heard at a meeting that Brigid Hogan and Saverio Bellusci were going to work on this problem, and I knew that they could do in a year what would take us five years to do. It was time to get out! During this time, I had been writing about evolutionary developmental biology, so I decided that this would be the context for my next research project. After mooting a number of possibilities, I decided that asking how the turtle got its shell would be a really good project, and we began collaborating with several bone developmental biology laboratories in the Philadelphia area. Many undergrads got their first research experience working on turtle embryos, and grad students working on serious human bone diseases could have some relief working with our turtles. We proposed a paracrine factor hypothesis for the origin of the carapace, and we have evidence that cells migrating the trunk neural crest may actually form the plastron. Many years later, I decided that if I really wanted to get answers to these questions, I had to get into a research laboratory. So, I went half-time at Swarthmore, and received a half-time position at the University of Helsinki, working in the lab of Jukka Jernvall. We’re still working on the turtle project. I no longer have a lab, but Judy Cebra-Thomas has really interesting data that, if confirmed, will give us a great story on how the turtle gets both its carapace and its plastron. Former student Tyler Lyson has been integrating our developmental data into the paleontological record to identify the mechanisms by which turtles may have evolved their shells. The turtle has gone from being an anomaly to being a prime example of how developmental biology and palaeontology can interact to construct an account of how organisms evolved. I’m presently pursuing work on holobiont development (discussed below).
Visual summary of Scott’s lecture at the Italian Society for Evolutionary Biology meeting in 2019 by Jacopo Sacquegno (jacoposacquegno.com)
Working at a liberal arts college such as Swarthmore, you’re expected to do research because it’s the best way of teaching your undergrads. Of course, you go a bit slower because you’re teaching methods and attitudes. (I know how to do an in situ hybridization; my job is to teach the students how to do it; and they do not get it right the first time.) Also, a teacher at a liberal arts college has the ability to work with people outside one’s own department. This has allowed me to publish on the aesthetics of embryology, the roles of puns in science education, the bone that the Bible says created Eve (it wasn’t a rib!), and the use of embryos in the art of Gustav Klimt and Frida Kahlo. My students and I have collaborated to publish papers on Intelligent Design (writing this paper was their final exam), temperature-sensitive holobionts (another final exam), and feminist critiques of biology (which was one of the first papers in the field). When I gave a history of biology course, I saw that the students’ term papers on bioethics would make a fascinating book. Why should I be the sole audience for these investigations? So, with two students as co-editors, we published it. All-in-all, I’ve published nearly 200 papers, many of them concerning the history, philosophy, and social situatedness of biology.
What drew you to the field of evo-devo, and now eco-devo?
My interest in evo-devo comes from my background in the history of embryology. I took a master’s in the history of embryology, and I had directed readings with Bill Coleman on the science of Thomas Huxley, with Camille Limoges on the biology of Sir Richard Owen, and with Donna Haraway on the history of embryology, where we discussed Waddington and others. This meant that I knew the background for evolutionary theory that came out of embryology; I was exapted for evo-devo. I knew about homology and about developmental notions of adaptation. I had read EB Wilson, Frank Lilly, Fritz Müller and Aleksander Kovalevsky. I knew about these people who had a developmental approach to evolutionary biology. In our 1996 paper, John Opitz, Rudolf Raff and I wrote that we can now return to these questions that we had abandoned, that we now have the techniques to go back and look at the notions of homology, look at the notions of heterochrony, look at these notions that we abandoned largely for genetics at the turn of the last century.
So, I was similarly pre-adapted for eco-devo. Again, I knew the history. I knew about the debates between Oscar Hertwig and August Weismann and the examples of developmental plasticity and context-dependent phenotypes. I was encouraged in this area by Donna Haraway, Evelyn Fox Keller and Anne Fausto-Sterling, who were railing against genetic determinism. I found that there was another embryologist who had retired to Swarthmore, NJ (Jack) Berrill. Berrill’s developmental biology books were amazing, and he was adamant that genetics could not explain development. So, I had all these people around me who were talking about environmental regulation of development. Then, in 2001 I had a ‘eureka moment’ when I read the article by Laura Hooper and her colleagues on bacteria controlling gene expression in the mouse intestine. It made me think that this was the missing piece, the influence of microbes on development. They showed that commensal bacteria induced angiogenin-4 production in our intestinal cells, and this secreted protein induced the adjacent mesoderm to become the blood vessels of the gut. This was not only a good thing for the mouse’s life, this protein also helped the microbes by killing Listeria and other competitors. Moreover, mice that lack bacteria are asocial. Their brains were different. In making the mice social, they created the conditions for mouse reproduction, which means not only more mice, but more bacteria.
I’ve become fascinated by the development and evolution of the holobiont, the organised consortium of symbionts. We humans are not only organisms but biomes. We develop with help from other species. How do we receive bacteria and how are they structured in the body? How do they induce the maturation of the gut neurons and the auditory neurons? How do they help mature the immune system, which then patrols our bodies? Does natural selection select ‘teams’ rather than individual players? Are we losing bacteria that are crucial for our normal development? These are new questions for developmental biologists, and they relate directly to environmental concerns.
How did you come to write the first version of ‘Developmental Biology’, which was published in 1985?
The first version was written out of frustration. I had just accepted the position of teaching developmental biology at Swarthmore, and I was frustrated because I had no book that I felt I could teach from. Developmental biology had changed; there were books on ectoderm, endoderm, and mesoderm, with scant mention that genes might be involved. Conversely, there were textbook on RNA, DNA, proteins in development, with only a hint that they somehow formed mesoderm etc. I wanted a view of developmental biology that would integrate classical embryology, cell biology, and molecular biology. Apparently, many other young developmental biologists were thinking the same way and the publishers realised this. So, in 1980, Andy Sinauer, the publisher of ‘Developmental Biology’, was trying to find a person to write such a book. He wanted David Sonneborn to write one, so he went to visit David at University of Wisconsin. According to David, he told Andy that he had a great lab, a great project, and grant money, so he wasn’t going to write such a book. But he said that there was this postdoc down the hall who’s been griping that he doesn’t have a textbook to teach from, and that maybe he should talk with him. So, I got to speak with Andy Sinauer, who suggested that I send him three sample chapters that he would send out for review. The summer before I came to Swarthmore, he gave me the go-ahead to write the book. I later found out that many other people had been thinking about writing textbooks for the same reason I did; but when my textbook came out, there was lateral inhibition. My textbook was similar enough to what they wanted, so they didn’t have to write their own books.
I owe a lot to Andy Sinauer and the fact he was willing to take a chance on me as a postdoc. It was five years before the book first came out. It actually took four years to write, but we had some delays. This ended up being a good thing, because in 1984/85, John Gerhart published his Nieuwkoop center articles, and Katherine Anderson published that maternal mRNA in Drosophila is important for the dorsal ventral axis patterning. The molecularisation of the field was really starting at this time, and I was able to get that into the book.
Another example of when working with a small publishing house was an advantage came in 1997. I was in the cafeteria at my college early in the morning, reading The New York Times. I had a really nasty moment. I don’t know what I yelled, but I immediately ran up to my office, called my editor, Carol Wigg, and asked her if the book manuscript had gone out to the printers yet. She told me that it was in the outbox and would go out that morning. I asked her to grab it and bring it back to her desk. She asked what had happened, and I said they cloned a sheep! We had specifically said in the book that no adult mammal had ever been cloned from a differentiated mammalian cell. Now it had been done; Dolly had arrived. Andy Sinauer called me back a few hours later and told me that I could have one sentence – 120 characters – to replace the sentence we had written earlier. So, when that book came out, about four months later, Dolly was in it!
With the field often moving so quickly, how do you decide what to update in each edition?
I update every chapter in the book (and with my new co-author, Michael Barresi, on board, I have fewer chapters to revise). The small revisions are made piecemeal. Usually, when I read something that I find interesting, I’ll write a paragraph about it and file it away. Then I can go back to it when I’m revising the chapter. Going to meetings is absolutely crucial for revising the chapters, because at meetings, especially at the poster sessions, bars, and meals, I’ll hear about the unpublished work. For instance, I first heard about the SRY gene from Albert de la Chapelle at a meal at a conference. The research hadn’t been published yet. That’s why, as good as Zoom is, it shouldn’t replace scientific meetings. Revising is also much easier now because of the internet. I used to have to go to the college library with my list of journals. I even had a key because I often got there before the librarians! Now, I go to PubMed or Web of Science, and I type in sea urchin fertilisation, chick gastrulation etc. and I’ll find things that I never would have seen by looking in journals.
The new chapters happen when there are big changes in the field. The evo-devo chapter came about from anger and bewilderment! I was at a meeting where some theoretical biologists were claiming that you can discuss evolution mathematically, without knowing about development or even the organism. I felt that this was clearly wrong, and so I put an evolution and development chapter into the book, giving examples of how evolution actually occurs by developmental changes. The ecological developmental chapter was written after a challenge by Cor van der Weele, who criticised my textbook at a meeting, saying that all my examples of developmental plasticity were in the ‘sidelights and speculations’ sections, literally marginalising them. I replied that there was no chapter on ecological development because there was no coherent theory linking these phenomena together, and I couldn’t write a chapter of mere episodes. Cor told me to find such a link. And that year (1995), three publications came out. Firstly, Lynn Nyhart’s book ‘Biology Takes Form’, showed me that the earliest experimental developmental biology was indeed eco-devo. Then, Jessica Bolker had a wonderful article on how the model organisms that we use in developmental biology were all chosen to reduce or eliminate environmental effects, so you could compare your results to the results between labs and highlight genetic causation. And then David Epel wrote that insightful paper, ‘Beakers versus breakers: how fertilisation in the laboratory differs from fertilisation in nature’, discussing how studying sea urchin fertilisation is in the laboratory was different from studying it in the field. At this point I thought, ok, I can now write a coherent chapter on the environment and development that would fit into the textbook.
To play devil’s advocate on your comment about information being so readily available on the internet: why is your textbook still important?
Textbooks summarise, organise, and synthesise an enormous amount of research. They also are de facto ‘gateways’ that interpret what is considered accurate scientific fact. This last is a problematic function because it can prevent new ideas from becoming accepted. However, I think that it’s more important than ever to have someone or some group vetting scientific information.There is so much garbage and misinformation on the web, especially if one is looking for information about fertilisation or human development. Initially, I hated the idea of textbooks being gatekeepers; but that’s what they’re becoming.I think textbooks are becoming an important resource inthe age of the internet and social media, where everybody can be a broadcasting company.In 1994, we started a website for the textbook so that researchers could update, disagree with, and download new information onto the website. We didn’t want the book to be a gatekeeper; we wanted it to be a community resource. We tried that for four years, but it didn’t work, people were not downloading anything. (We had a Quadra 950 computer that could hold 16 people at a time, and a LaCie storage disc that could hold 1 entire gigabyte of information! Yes, it crashed.) But I think, as the internet has become a huge part of our lives, the idea of vetting information has become critically important in science. So, I think that in a crazy way, textbooks have increased in importance.
What’s new in the upcoming (13th) edition of ‘Developmental Biology’?
We have two new and important chapters. One new addition comes straight after the chapter on fertilisation and gives an overview of early development throughout the animal and plant kingdoms. So, before going into the details of sea urchin, Drosophila, chicken, mammalian development, we provide the reader an overview of cleavage and gastrulation, and how it’s done. We talk about the mechanics of cell division, convergent extension, all these things that are going on in different ways in the different phyla. The idea is that we show the forest before we show the trees. The second new chapter is on human embryology. The inclusion of this chapter allows us to discuss things that we couldn’t detail in the mammalian development section. For instance, we can now detail the research on implantation and discuss the fascinating studies on how the embryo and the uterus interact during development. It also meant that we could bring forth some of the bioethics issues. For instance, we talk about when human life begins and also about what is ‘normal.’ (We found eight definitions of what is normal in the biomedical literature.) This chapter will be provocative. It should make people question their ideas. It may not change them, but I think it will give students something to think about and something to talk to their roommates and families about.
How has writing the book changed since Michael Barresi came onboard as your co-author?
The book has benefitted enormously from Michael’s passions and expertise. He is uniquely qualified, as he is pleasantly obsessed by those areas of developmental biology that are growing in importance – developmental neurobiology, environmental disruptions, and stem cells. He has been adamant that plants be fully represented, and that human embryology be a separate chapter. Michael is also doing pioneering work in electronic pedagogy and has helped keep developmental biology teachers active during the Covid-19 pandemic. He is using such electronic pedagogy to show students that developmental biology is an international, interracial, intergender discipline, and that anyone in his class should feel comfortable going into it. He has become the point person for the e-book and for the web-based material. Michael is also teaching classes (whereas I am retired), so he gets immediate feedback from his students, which is invaluable.
What do you think are the next big questions for developmental biologists?
I obviously think that ecological developmental biology is going to be enormously important because it addresses some of the problems of climate change. Climate change is happening, and developmental biology belongs in the context of climate change: what is going to happen to turtles (who have temperature-dependent sex determination), what is going to happen to coral reefs (where the life of the coral depends on its endosymbiotic algae)? What happens to the interactions between plants and their pollinators if a flower’s sexual development is determined by photoperiod, and the pollinators’ eclosion depends on temperature? These all depend on development.
Related to that, I think that studying plant and fungal development is becoming even more important. Our foods, our building materials, perhaps even our energy sources, may be coming from modified plants and fungi. Knowledge of plant and fungal development may be critical for all life on this planet.
Thirdly, I think that brain development will always be one of the great frontiers of developmental biology. As Young Frankenstein says, “Hearts and lungs are simply tinker toys when stacked against the brain!” Liver cells have may have a dozen or so connections to other cells, while brain neurons can have 105 such connections. How are these organized?
Then of course, there is evo-devo. I think that if we are going to discuss the origins of biodiversity seriously, then we have to discuss evo-devo. Nothing about evolution makes sense except in the light of developmental biology. If one wants to talk about how variations occur, you need developmental biology. I’ve started to think about evo-devo in terms of it being the holobiont that is evolving and developing. Then the question becomes: What happens when an organism acquires a new symbiont, does that give it a different phenotype? (We know that some of our agricultural pests used to be rather benign critters until they found a different symbiont, for example the red turpentine beetle, it wasn’t a pest until it found a different fungus.) Our genome has and uses several genes from retroviruses, and some beetles seem to have acquired genes for cellulose digestion from symbiotic fungi. Acquiring symbionts was critical for the evolution of herbivory, and the bacteria helps the bovine rumen to develop! So, looking at the evolution of the holobiont in an evo-devo way is going to be really interesting, and very important.
Finally, is there anything that the Node community might be surprised to find out about you?
I have played piano in a klezmer band and have given concerts of “Schlock Rock of the 60s.” My teaching philosophy comes largely from what Leonard Bernstein said when he was asked why he conducted so much of Mahler’s music. Bernstein replied that since he loves Mahler and loves his audience, he wanted his audience to love Mahler as much as he did. It’s easy to transfer that to developmental biology.
Muhammed Simsek, Ertuğrul Özbudak and colleagues have discovered that oscillations in the ppErk gradient, driven by the Her1-Her7 oscillator, is sufficient for sequential segmentation during zebrafish somitogenesis. Muhammed, Angad, Didar and Ertuğrul share the story behind their research, which was recently published in Nature.
How did you get started on this project?
E.M.Ö.: We are broadly interested in the mechanisms governing spatiotemporal control of somite segmentation. Sequential formation of those embryonic tissues is a landmark example of developmental pattern formation. How this process is controlled in space and time has long been debated. In this project we aimed to tackle this long-standing question. To put it in a framework, maybe I should give a brief description of the field’s status quo first.
Yes, please…
E.M.Ö.: Among its alternatives, the clock and wavefront (CW) model dominated the field and became the textbook model as some evidence suited this model the best. The CW model was initially proposed approximately 50 years ago1. Seminal works by the Olivier Pourquie’s lab, who was my second postdoctoral mentor, identified critical molecular players controlling somite segmentation. Although the dynamics of discovered segmentation clock genes2 and signalling gradients3 were different than how they were envisioned in the original CW model, Olivier noticed that his discoveries could be better explained by an updated version of the CW model than other competitive conceptual models in the field. Therefore, he updated the CW model to its current form in the textbooks4. According to this later version of the CW model (let’s call it CWL, L for later), a molecular clock controls the period of segmentation while posteroanterior FGF/ppERK and/or Wnt/β-Catenin gradients determine the positions of segment boundaries. According to the CWL model: (1) the clock and the gradient act independently, (2) how cells integrate their information is unknown, (3) the gradient passively moves over cells posteriorly by tail elongation, is static in the tailbud frame, and provides positional information at a concentration-threshold.
Where did the CW model fall short of explaining things?
E.M.Ö.: While I was completing my first postdoctoral study in the late Julian Lewis’s lab, Kageyama lab published a seminal paper showing that ppERK gradient is not static but rather its amplitude (peak levels) and spatial range oscillates in the mouse PSM by carefully sorting static ppERK immunostaining data5. This clearly violated the static gradient and smoothly regressing wavefront of the CWL model. It was also counterintuitive that an oscillatory gradient could reliably encode positional information at concentration-thresholds. We (Julian and Ertuğrul) were disturbed with the implications of new findings; other colleagues in the field might have shared the same feelings. Additional data, specifically from Aulehla Lab, came out later that also did not seem to fit to the CW model. Although these results shook our trusts in the CWL model, a better model did not emerge.
One option to save the CWL model was to attribute the main wavefront function to the Wnt/ β-catenin gradient instead of the FGF/ppERK one. There is positive feedback between the FGF/ppERK and Wnt/β-Catenin gradients in the posterior PSM and perturbing the activities of each one changes the somite lengths. Wnt/ β-catenin gradient has not been shown to oscillate yet. Thus, it is theoretically possible that Wnt/β-Catenin gradient (if it is not oscillating) directly encodes the positional information while the FGF/ppERK gradient affects somite lengths indirectly through the Wnt/β-Catenin gradient. Therefore, it was critical for us to first find out which gradient directly instructs positional information. This was the first project Muhammed undertook after joining my lab for postdoctoral training.
M.F.S.: I had joined the lab with exposure to cell culture and microscopy. So, I was working on developing a 3-D explant culture for near-objective imaging of zebrafish tails without yolk6. One day I accidentally noticed some explants had stopped their axis elongation but kept making smaller and smaller somites. Decoupling axis elongation from gradient dynamics, we had a perfect tool to test what “the positional information” was for somites. We published those results from both explants and whole embryos in our 2018 study7, which set the foundation of our recently published paper8. In the 2018 paper, we showed that FGF/ppERK gradient directly instructs positional information for somites while Wnt/β-Catenin indirectly influences somite boundaries by its coupling with the FGF/ppERK gradient. To our surprise, we also discovered this instruction however was not at a fixed concentration threshold of the gradient and was not cell-autonomous. Instead, cells compare their ppERK levels with their neighbours and boundaries are instructed when the neighbour comparison passes a critical ratio (the spatial fold-change, SFC). This is mathematically equivalent to local gradient slope divided by local ERK activity.
E.M.Ö.: After this work, several new questions emerged: (1) How could ERK activity universally encode positional information if its dynamics are not conserved among the vertebrates? (2) If it was conserved, that is if ERK activity had also oscillated in zebrafish like mice, how can this oscillatory gradient reliably encode positional information? (3) Why is this ratiometric (SFC) signal encoding utilized instead of a simple concentration-threshold (i.e., what’s the advantage of the SFC over concentration threshold)? (4)How the clock and ERK activity gradient are integrated? We reported our answers to these critical questions in the recently published paper.
Can you summarise your findings?
E.M.Ö.: In this work, we first showed that ppERK gradient is not static but rather oscillating in zebrafish as well. This points to a conserved ppERK dynamics among vertebrates. We then showed that ppERK oscillations are clock-dependent and that the clock, by periodically repressing ppERK levels, projects its oscillations on the gradient. Building upon this knowledge, we were able to create boundaries in clock mutant fish (these fish lack clock genes and hence no proper somite boundaries form) by artificially repressing ppERK levels in a periodic manner using pharmacological drugs. These results also broke a long-standing dogma in the field regarding the role of traveling waves of the segmentation clock, showing that they are dispensable for the somite formation. Crucially, it resolved the hierarchy of the somitogenesis network. Unlike the CW model proposed, the clock actually works upstream of FGF signalling. Our results further showed that as long as ERK activity is periodically repressed somite boundaries can be formed.
When doing the research, did you have any particular result or eureka moment that has stuck with you?
A.S.C.: For an aspiring young scientist like me, it was the use of systems approach to resolve this decades old problem of pattern formation. Taking part in this project, I closely witnessed the power of systems approach in teasing out the working principles of nature. Especially, when Ertuğrul and Muhammed came up with an experiment to test if the clock’s only role in boundary formation is to periodically repress ERK activity. At first, I was not able to believe the results but once repeated, it was an eureka moment for me. While reading the stories of discoveries, I was always amazed by the feeling that there were secrets of nature known only to the researchers. Working on this project gave a me a taste of how that felt.
M.F.S.: We first simulated this pulsatile drug inhibition idea to see if imitating the clock’s action with drugs was really feasible. Affirmative outcome was a big motivation for experimentally searching for the optimal treatment regimen. Those days were joyful that I was seeing chevron shape somite boundaries even in clouds and kept spamming lab’s chat group with pictures of drug-induced somites.
D.S.: As a graduate student in biology with a background in physics, I am trained to use math to derive answers in physics and my curiosity brought me into biology where most complex molecular mechanisms take place. While working on this project, it was amazing to see how the predicted dynamics was emerging bit by bit from every experimental data. I was blown-away seeing how mathematical modelling can predict the function of biological signalling pathways in developing embryo.
And what about the flipside: any moments of frustration or despair?
M.F.S.: The dynamics we were quantifying were quite fast that not having a live ERK activity reporter to capture it was kind of frustrating. I think Angad did a perfect job at implementing kinase translocation reporters developed for ERK signalling to generate a zebrafish line. It was satisfying to see the cytoplasmic localization of the live reporter was perfectly capturing underlying ppERK gradient.
A.S.C.: Live imaging of double reporter (the segmentation clock and ERK activity) was quite challenging. Segmentation and tracking of single cells of presomitic mesoderm (PSM) was turning out to be an impossible task, given that cells are quite dynamic, motile and have relatively large nuclei. Muhammed and I had to manually verify each software-tracked cell.
Where will this story take the lab?
E.M.Ö.: One big question remained in this work was how the clock molecularly and mechanistically regulate the ERK activity. It is quite surprising that the clock, known as a bHLH family transcriptional repressor, can lower ppERK levels quite speedily. We are currently working on this aspect of the problem. Another direction is discovering the decoding mechanism that cells use to understand SFC dynamics and execute the boundary-making decision.
What is next for you after this paper?
E.M.Ö.: Muhammed is looking for a place to establish his own lab where he will work on similar problems. Others in the lab will continue working on non-overlapping problems.
M.F.S.: I want to understand the design principles behind how position is sensed in embryos and why sequential segmentation is so widespread in animal body plans. Somitogenesis has been and will continue to be my main sandbox to play with those ideas.
A.S.C.: This work has furthered my interest in science and especially about those moments when you are one of the lucky few whom nature reveals how it works. I feel more very passionate to finish my own projects which also deals with similar fundamental questions.
D.S.: This project has been a fascinating experience for me to see the conference of biology and mathematical modelling which motivates me to further understand how embryos form spatiotemporal patterns by encoding and interpreting biological signals in real-time.
REFERENCES
1. Cooke, J. & Zeeman, E. C. A clock and wavefront model for control of the number of repeated structures during animal morphogenesis. J Theor Biol58, 455–476 (1976).
2. Palmeirim, I., Henrique, D., Ish-Horowicz, D. & Pourquié, O. Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis. Cell91, 639–648 (1997).
3. Dubrulle, J., McGrew, M. J. & Pourquié, O. FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell106, 219–232 (2001).
4. Hubaud, A. & Pourquié, O. Signalling dynamics in vertebrate segmentation. Nat Rev Mol Cell Biol15, 709–721 (2014).
5. Niwa, Y. et al. The Initiation and Propagation of Hes7 Oscillation Are Cooperatively Regulated by Fgf and Notch Signaling in the Somite Segmentation Clock. Dev Cell13, 298–304 (2007).
6. Simsek, M. F. & Özbudak, E. M. A 3-D Tail Explant Culture to Study Vertebrate Segmentation in Zebrafish. Journal of Visualized Experiments2021, e61981 (2021).
7. Simsek, M. F. & Özbudak, E. M. Spatial Fold Change of FGF Signaling Encodes Positional Information for Segmental Determination in Zebrafish. Cell Rep24, 66-78.e8 (2018).
8. Simsek, M. F. et al. Periodic inhibition of Erk activity drives sequential somite segmentation. Nature613, 153–159 (2023).
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