“By and large, animals have the same genes that you and I have. They’re just using them in a different way that makes it less likely for them to get a disease.”
Dr Linda Goodman, Fauna Bio
In the latest episode of Genetics Unzipped, we’re becoming chromosomal criminals and learning about how researchers are stealing genes from the animal kingdom and using them to improve human health. From 13-lined ground squirrels teaching us how to recover from heart attacks, to bowhead whales showing us how to avoid cancer, there’s a lot geneticists can learn from Mother Nature.
Now in its thirteenth year of serving the developmental and stem cell biology community, the Node continues to be the place for scientists to share research stories, job adverts and event listings. Helen Zenner (previous Community Manager of the Node, now at FocalPlane) and Katherine Brown (Development Executive Editor) recently wrote an Editorial in the journal Development, reviewing some of the Node’s most popular features, as well as introducing some of our newer initiatives.
One highlight for 2023 is the correspondents scheme, a joint project with our sister site FocalPlane (find out more about FocalPlane in this companion Editorial in Journal of Cell Science). For the Node, we have appointed Alexandra Bisia (University of Oxford), Brent Foster (University of Florida) and Dina Myasnikova (University of Tokyo) as the Node correspondents. You can find out more about Alexandra, Brent and Dina in our interviews on the Node, and find their posts collected together at https://thenode.biologists.com/the-node-correspondents/.
The Node Correspondents
The Node only works because of the fantastic engagement from all of you in the developmental and stem cell biology community. Thank you for reading, posting, and contributing to the Node over the years. If you have any ideas or feedback for the Node, don’t hesitate to email us at thenode@biologists.com. Remember, once you are registered with the Node, you are free to contribute, post and comment on the site!
Joseph J Hanly, Ling S Loh, Anyi Mazo-Vargas, Teomie S Rivera-Miranda, Luca Livraghi, Amruta Tendolkar, Christopher R Day, Neringa Liutikaite, Emily A Earls, Olaf BWH Corning, Natalie D’Souza, José J Hermina-Perez, Caroline Mehta, Julia Ainsworth, Matteo Rossi, W. Owen McMillan, Michael W Perry, Arnaud Martin
Shuyao Kong, Mingyuan Zhu, M. Regina Scarpin, David Pan, Longfei Jia, Ryan E. Martinez, Simon Alamos, Batthula Vijaya Lakshmi Vadde, Hernan G. Garcia, Shu-Bing Qian, Jacob O. Brunkard, Adrienne H. K. Roeder
Moises Freitas-Andrade, Cesar H Comin, Peter C Van Dyken, Julie Ouellette, Joanna Raman-Nair, Nicole Blakeley, Quing Yan Liu, Sonia Leclerc, Youlian Pan, Ziying Liu, Micael Carrier, Karan Thakur, Alexandre Savard, Gareth M Rurak, Marie-Eve Tremblay, Natalina Salmaso, Luciano Da F Costa, Gianfilippo Coppola, Baptiste Lacoste
Andrew J Aman, Lauren M Saunders, August A Carr, Sanjay R Srivatsan, Colten Eberhard, Blake Carrington, Dawn E Watkins-Chow, William Pavan, Cole Trapnell, David M. Parichy
Benjamin T. Throesch, Muhammad Khadeesh bin Imtiaz, Rodrigo Muñoz-Castañeda, Masahiro Sakurai, Andrea L. Hartzell, Kiely N. James, Alberto R. Rodriguez, Greg Martin, Giordano Lippi, Sergey Kupriyanov, Zhuhao Wu, Pavel Osten, Juan Carlos Izpisua Belmonte, Jun Wu, Kristin K. Baldwin
Martin Minařík, Melinda S. Modrell, J. Andrew Gillis, Alexander S. Campbell, Isobel Fuller, Rachel Lyne, Gos Micklem, David Gela, Martin Pšenička, Clare V. H. Baker
Edward J. Grow, Ying Liu, Zhiqiang Fan, Iuri Viotti Perisse, Tayler Patrick, Misha Regouski, Sean Shadle, Irina Polejaeva, Kenneth L. White, Bradley R. Cairns
Chengxiang Qiu, Beth K. Martin, Ian C. Welsh, Riza M. Daza, Truc-Mai Le, Xingfan Huang, Eva K. Nichols, Megan L. Taylor, Olivia Fulton, Diana R. O’Day, Anne Roshella Gomes, Saskia Ilcisin, Sanjay Srivatsan, Xinxian Deng, Christine M. Disteche, William Stafford Noble, Nobuhiko Hamazaki, Cecilia B. Moens, David Kimelman, Junyue Cao, Alexander F. Schier, Malte Spielmann, Stephen A. Murray, Cole Trapnell, Jay Shendure
Ivan Imaz-Rosshandler, Christina Rode, Carolina Guibentif, Mai-Linh N. Ton, Parashar Dhapola, Daniel Keitley, Ricard Argelaguet, Fernando J. Calero-Nieto, Jennifer Nichols, John C. Marioni, Marella F.T.R. de Bruijn, Berthold Göttgens
Anoushka Joglekar, Wen Hu, Bei Zhang, Oleksandr Narykov, Mark Diekhans, Jennifer Balacco, Lishomwa C Ndhlovu, Teresa A Milner, Olivier Fedrigo, Erich D Jarvis, Gloria Sheynkman, Dmitry Korkin, M. Elizabeth Ross, Hagen U. Tilgner
Hisato Yagi, Cheng Cui, Manush Saydmohammed, George Gabriel, Candice Baker, William Devine, Yijen Wu, Jiuann-huey Lin, Marcus Malek, Abha Bais, Stephen Murray, Bruce Aronow, Michael Tsang, Dennis Kostka, Cecilia W. Lo
Left-right differential gene expression from Yagi et al.
David Bolumar, Javier Moncayo-Arlandi, Javier Gonzalez-Fernandez, Ana Ochando, Inmaculada Moreno, Carlos Marin, Antonio Diez, Paula Fabra, Miguel Ángel Checa, Juan José Espinos, David K. Gardner, Carlos Simon, Felipe Vilella
Nana Matoba, Brandon D Le, Jordan M Valone, Justin M Wolter, Jessica Mory, Dan Liang, Nil Aygün, K Alaine Broadaway, Marielle L Bond, Karen L Mohlke, Mark J Zylka, Michael I Love, Jason L Stein
Heather L. Dingwall, Reiko R. Tomizawa, Adam Aharoni, Peng Hu, Qi Qiu, Blerina Kokalari, Serenity M. Martinez, Joan C. Donahue, Daniel Aldea, Meryl Mendoza, Ian A. Glass, Birth Defects Research Laboratory (BDRL), Hao Wu, Yana G. Kamberov
Daniela Doda, Sara Alonso Jimenez, Hubert Rehrauer, Jose F. Carreño, Victoria Valsamides, Stefano Di Santo, Hans Ruedi Widmer, Albert Edge, Heiko Locher, Wouter van der Valk, Jingyuan Zhang, Karl R. Koehler, Marta Roccio
Florentine Dylong, Jan Riedel, Gaurang M. Amonkar, Nicole Peukert, Paula Lieckfeldt, Katinka Sturm, Benedikt Höxter, Wai Hei Tse, Yuichiro Miyake, Steffi Mayer, Richard Keijzer, Martin Lacher, Xingbin Ai, Jan-Hendrik Gosemann, Richard Wagner
Clara Morral, Arshad Ayyaz, Hsuan-Cheng Kuo, Mardi Fink, Ioannis Verginadis, Andrea R. Daniel, Danielle N. Burner, Lucy M. Driver, Sloane Satow, Stephanie Hasapis, Reem Ghinnagow, Lixia Luo, Yan Ma, Laura D. Attardi, Costas Koumenis, Andy J Minn, Jeffrey L. Wrana, Chang-Lung Lee, David G. Kirsch
Shruthi Subramanian, Julie A.I. Thoms, Yizhou Huang, Paola Cornejo, Forrest C. Koch, Sebastien Jacquelin, Sylvie Shen, Emma Song, Swapna Joshi, Chris Brownlee, Petter S. Woll, Diego Chacon Fajardo, Dominik Beck, David J. Curtis, Kenneth Yehson, Vicki Antonenas, Tracey O’ Brien, Annette Trickett, Jason A. Powell, Ian D. Lewis, Stuart M. Pitson, Maher K. Gandhi, Steven W. Lane, Fatemeh Vafaee, Emily S. Wong, Berthold Göttgens, Hamid Alinejad Rokny, Jason W.H Wong, John E. Pimanda
Ambre Guillory, Mauricio Lopez-Obando, Khalissa Bouchenine, Philippe Le Bris, Alain Lécureuil, Jean-Paul Pillot, Vincent Steinmetz, François-Didier Boyer, Catherine Rameau, Alexandre de Saint Germain, Sandrine Bonhomme
Brennan Hyden, Dana L. Carper, Paul E. Abraham, Guoliang Yuan, Tao Yao, Leo Baumgart, Yu Zhang, Cindy Chen, Ronan O’Malley, Jin-Gui Chen, Xiaohan Yang, Robert L. Hettich, Gerald A. Tuskan, Lawrence B. Smart
Juliane Tschuck, Vidya Padmanabhan Nair, Ana Galhoz, Gabriele Ciceri, Ina Rothenaigner, Jason Tchieu, Hin-Man Tai, Brent R. Stockwell, Lorenz Studer, Michael P. Menden, Michelle Vincendeau, Kamyar Hadian
Robert Hardt, Alireza Dehghani, Carmen Schoor, Markus Gödderz, Nur Cengiz Winter, Shiva Ahmadi, Ramesh Sharma, Karin Schork, Martin Eisenacher, Volkmar Gieselmann, Dominic Winter
Ran Wang, Xianfa Yang, Jiehui Chen, Lin Zhang, Jonathan A. Griffiths, Guizhong Cui, Yingying Chen, Yun Qian, Guangdun Peng, Jinsong Li, Liantang Wang, John C. Marioni, Patrick P.L. Tam, Naihe Jing
Soumyaroop Bhattacharya, Caroline Cherry, Gail Deutsch, Birth Defects Research Laboratory (BDRL), Ian A. Glass, Thomas J. Mariani, Denise Al Alam, Soula Danopoulos
Tomas Wald, Adya Verma, Victoria Cooley, Pauline Marangoni, Oscar Cazares, Amnon Sharir, Evelyn J. Sandoval, David Sung, Hadis Najibi, Tingsheng Yu Drennon, Jeffrey O. Bush, Derk Joester, Ophir D. Klein
Luca Deininger, Sabine Jung-Klawitter, Petra Richter, Manuel Fischer, Kianush Karimian-Jazi, Michael O. Breckwoldt, Martin Bendszus, Sabine Heiland, Jens Kleesiek, Ralf Mikut, Daniel Hübschmann, Daniel Schwarz
Cheng-Yu Li, Helena Boldt, Emily Parent, Jax Ficklin, Althea James, Troy J. Anlage, Lena M. Boyer, Brianna R. Pierce, Kellee Siegfried, Matthew P. Harris, Eric S. Haag
Dr Liam Barry-Carroll, Dr David A Menassa, Professor Diego Gomez-Nicola and colleagues have recently published a paper in Cell Reports elucidating the mechanisms by which microglial cells expand as a population in the mouse brain using fate-mapping approaches. We asked Dr Barry-Carroll to give us a behind the scenes look into how the story came together.
How did you get started on the project?
I started working on the project when I joined the Gomez-Nicola lab in 2017 to start my PhD. I had been interested in studying microglia and so I applied for the position on a website called findaphd.com and was lucky to be accepted. For me it was interesting to study the cells in a healthy context which can be so often overlooked in the field.
What was already known about microglial colonisation and expansion in rodents?
Studies coming out in the 1990s were able to demonstrate that progenitors of microglia were highly proliferative and subsequent studies had shown that a relatively small number of microglia progenitors go on to colonise the entire brain in just a short timespan during early postnatal life. However, it was unknown whether this was through clonal expansion or whether it was a more stochastic process of random proliferation of all the cells, as is the case of microglia in the healthy adult brain. Interestingly we can gain some insight from disease models whereby fate mapping studies have demonstrated that microglia will clonally expand in response to injury or disease. Our goal here was to see which of these potential mechanisms is responsible for the developmental colonisation of the brain by microglia.
Can you summarise your findings?
Here we were able to build on the findings of previous studies and showed that microglia expand quite rapidly, particularly during early development and that this expansion is correlated with the growth of the brain. As development continues, we could see changes in the spatiotemporal distribution of microglia from more dense clusters until late postnatal development (P21) when they formed a tiled or mosaic distribution allowing them to really cover the entire cortex and parenchyma. Using two methods of fate mapping, we demonstrated that microglial progenitors clonally expand during embryonic and postnatal development. Our multicolour lentiviral labelling approach allowed us to carry out clone-by-clone analysis and we observed that the mosaic of microglia is made up of inter-locking clones ranging in size from a couple of cells to quite large clones, indicating a disparity in the proliferative rate of different microglial progenitors during development. Subsequent mathematical modelling confirmed our finding that the proliferative potential is heterogenous among microglial progenitors. Another interesting finding was that microglia from larger clones tended to be spatially associated which may result in clonal dominance in certain brain regions.
Figure 1 Summary of experimental methods used to show how microglia expand in the mouse brain.
When doing your research, did you have a eureka moment that has stuck with you?
For me, the moment came when I applied the spatial analysis to the different experimental setups, that is when we could clearly see the same spatial trends present in our different set-ups.
What about the flipside? Any moments of despair or frustration?
There were some moments of despair, particularly in the beginning when we were testing different multicolour reporters to much less avail. Eventually it came down to a promoter that was not efficiently expressed in microglia. We managed to overcome this hurdle by setting up the sparse-labelling protocol as suggested by Dr Salah Elias (University of Southampton) who is a developmental scientist.
Where will this story take you next?
For now, I have finished this project and started a postdoc in the Nutrineuro laboratory in Bordeaux, France. However, I cannot say that I wouldn’t like to revisit this topic in the future, and I hope that our study will inspire some more research into this area, particularly in understanding the molecular mechanisms involved in the regulation of microglial proliferation and the potential sources of this proliferative heterogeneity.
What is next for you after this paper?
As I said, I have recently started my journey as a postdoc with Dr Jean-Christophe Delpech and Dr Sophie Layé and I am applying my knowledge of microglia in the field of extracellular vesicles. I am really looking forward to seeing how I can combine these different research topics and all that I have learned and ultimately build my future research career. Exciting times ahead!
We are in the Faculty of Biology, Medicine and Health at the University of Manchester.
Research summary
Hilary Ashe: We aim to understand how cell signalling and gene expression dynamics control developmental patterning, using the Drosophila embryo and ovarian germline stem cells as models.
The Ashe lab
Lab roll call
Catherine Sutcliffe, Research Technician, provides lab support and contributes to research projects including germline stem cell regulation in the Drosophila ovary.
Lauren Forbes Beadle, Postdoctoral research associate, studying how dynamic transcription underpins developmental processes in the early Drosophila embryo.
Nabarun Nandy, Postdoctoral research associate, studying the genetic and cellular mechanisms responsible for Drosophila ovarian germline stem cell maintenance.
Alastair Pizzey, Postdoctoral research associate, studying translation dynamics in the early Drosophila embryo, using single molecule imaging.
Jennifer Love, PhD student, using quantitative approaches to investigate the role of mRNA degradation in early Drosophila development.
Gareth Moore, PhD student, studying the extracellular regulation of Bone Morphogenetic Protein Signalling in development and disease.
Favourite technique, and why?
Hilary: In situ hybridisation as I think it is amazing to be able to visualise tissue specific expression patterns throughout development. I love how it has stood the test of time, evolving to allow single mRNA imaging and spatial transcriptomics.
Apart from your own research, what are you most excited about in developmental and stem cell biology?
Hilary: The progress in, and potential for, dissecting patterning and morphogenesis in synthetic embryos, including human embryoids, is very exciting. I also like how cross species comparisons of developmental processes in organoids from different species are being used to study developmental timing.
How do you approach managing your group and all the different tasks required in your job?
Hilary: In addition to our weekly lab meeting, I meet individually with everyone in the lab once a week to discuss their projects. Juggling all the different tasks is always a challenge but I try to protect blocks of time for research-related tasks and keep on top of everything with a to do list of priorities.
What is the best thing about where you work?
Hilary: Great core facilities and some fantastic colleagues doing really interesting research.
Cath: The facilities and resources which are available at the University including Bioimaging and the Fly Facility
Lauren: Collaborative and friendly research environment.
Nabarun: Warm, friendly and extremely supportive environment alongside the easy access to cutting edge tools for cellular and molecular studies.
Ali: The collaborative environment and the facilities, particularly the selection of microscopes.
Jenny: Lots of opportunities to get involved in widening participation and social causes at UoM.
Gareth: The breadth of research going on at Manchester means there’s always someone to talk to, to solve a problem or try a new idea.
What’s there to do outside of the lab?
Hilary: Manchester has everything except a beach!
Cath: Close to the peak district, restaurants, football, museums
Lauren: The variety of cuisines/restaurants and live music.
Nabarun: Cosmopolitan culture of the city offers a huge range of places to explore and eat.
Ali: Excellent places for music, coffee and beer.
Jenny: Manchester has something for everyone from creatives, with the lively music and arts scene, to the more outdoorsy folk getting lost in the peak district.
Gareth: Finding the best coffee in Manchester (an endless joy) and access to great hiking (joyless if unending).
Browse through other ‘Lab meeting’ posts featuring developmental and stem cell biology labs around the world.
I think there was concerns about it being a big project and being big science and team science that, you know, worked well for Apollo missions, that worked well in physics and chemistry, but you know, biomedical researchers up until that point, never did big science projects. They were just unheard of.
Dr Eric Green
Earlier this week was DNA Day, which this year marks both the 20th anniversary of the Human Genome Project’s completion and the 70th anniversary of the discovery of the DNA double helix. To celebrate, we are rereleasing an episode from Series 3, when Kat interviewed the director of the US National Human Genome Research Institute, Dr Eric Green about his work on the Human Genome Project from its very inception.
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
In the second episode of the Human Developmental Biology Initiative’s new podcast, Made the Same Way, science historian Nick Hopwood meets with artist Princess Ari (aka B!TEZ) to discuss how we studied human development in the past and how this field of science is different today.
Throughout the episode, the pair will write and record an original piece of music inspired by their meeting, exploring science in a brand new way.
“Human embryology tells us all where we come from.”
– Professor Nick Hopwood
About the participants
Nick Hopwood is Professor of History of Science and Medicine in the Department of History and Philosophy of Science, University of Cambridge, and a deputy chair of Cambridge Reproduction. He is, most recently, the author of Haeckel’s Embryos: Images, Evolution, and Fraud (Chicago, 2015), which won the Levinson Prize of the History of Science Society, and co-editor of Reproduction: Antiquity to the Present Day (Cambridge, 2018), which is available as a highly illustrated paperback. He has finished a history of human embryos and holds a Leverhulme Major Research Fellowship to write The Many Births of the Test-Tube Baby, a history of claims to IVF. He is a keen walker, runner and gardener.
Princess Arinola Adegbite, professionally known as B!TEZ is a trip-hop singer and rapper from Manchester. The songstress fuses rap, Alternative pop, soulful vocals, and witty spoken word into her Afro-futuristic tracks. She draws inspiration from Nina Simone, FKA Twigs, No Name, Bjork, and Mazzy Star.
B!TEZ is also a multi-award-winning poet, filmmaker, and BBC Words First artist. In 2022 Marco Sebastiano Alessi praised her as an “inventive polymath”. She was awarded Manchester Young Creative of The Year by the Culture Awards for her artistic contributions to the city. She has been commissioned by Selfridges, BBC, British Triathalon, and the University of Cambridge amongst others. She has performed music at Sounds from the Other City, Band on The Wall, Soup Manchester, and the Blues Kitchen. B!TEZ is an MIF Sounds and Youth Music Next Generation Artist. Her debut single ‘Be Like You’ explores the internet’s influence on our identities and self-esteem. The single is from her EP Vintage Destiny and uses organic and electronic sounds to explore the relationship between nature and technology, out on 26/05/2023.
Please subscribe and listen on Apple podcasts, Spotify, or wherever you get your podcasts. If you enjoy the podcast, please rate and review us on Apple podcasts to help others find us!
Welcome to #devbiolstories, which I hope will grow into a wholly random collection of short pieces on stuff I want to write about. I also hope you’ll enjoy it.
Today, it’s #devbiolstories Assistant Professor Edition, in which I’ll highlight the work of some of the great new labs in #devbiol. Today, we’ll highlight Erica Hutchins, whose fledgling lab studies chick embryos (get it!) at UCSF. She’s keen to understand neural crest development and how it might go awry in human disease.
I really enjoyed reading Erica’s awesome preprint with Mike Piacentino and Marianne Bronner about P-bodies and RNA processing in EMT of the neural crest, because I’ve been curious lately about the weird myriad of RNA-based punctae/foci/dots in cells. Erica’s preprint speaks to the awesome power of modern chick embryology. So, today’s story is about chickens and the role they played at what we might call the very dawn of mechanistic developmental biology. It opens, surprisingly enough, with the death of Guy Fawkes.
On January 31st, 1606, Guy Fawkes famously broke his neck and so avoided being hung, drawn, and quartered, the brutal sentence handed down for his part in the failed “gunpowder plot” to overthrow the British government. Just a day before, however, his young co-conspirator Everard Digby was not so lucky. Only twenty-eight years old, Digby’s gruesome death left a wife and two young sons traumatized and destitute. For the older son, Kenelm, it was only the first episode in a lifetime of extreme drama.
As the Mayflower was sailing to America in 1620, Kenelm was being expelled from Oxford. He would become a renowned fencer in Italy, personally raid the ships of England’s enemies from Gibraltar to Turkey, and galivant through Paris with René Descartes. He fled Paris to escape the affections of the Queen of France (or so he claimed, escaping retribution for killing a French nobleman in a duel must also have been on his mind). It all caught up to him, though, and he spent two years in an English prison. He was also a developmental biologist.
In prison, Digby worked up a sweeping theory of the natural world, which he published in his 1644 Two Treatises. Influenced by the rational, mechanical thinking of his friend Descartes, the book’s three chapters on embryology make for astonishing reading.
In the previous story, we learned that chickens have driven #devbiol for millennia, but it was Digby who was the first to use artificial incubation to study them. Everyone since Aristotle had incubated their chicks under hens. Aided by Sir John Heydon (“that generous and knowing Gentleman”), Digby built a chick incubator with which “you may lay several eggs to hatch; and by breaking them out at several ages, you may distinctly observe every hourly mutation in them, if you please.” We do please, Kenelm!
More important by far, however, is that Digby’s studies of the chick led him not only to describe development as others had done before him, but to explain it. As such, the Two Treatises provide one of the very first attempts at what we might call a “mechanistic” explanation of development. Clearly, he was gunning for a top journal.
Digby arrived at his novel idea about development (which was at the time called “generation”) by cleverly “considering how a living creature is nourished.” He wonders:
“Why should not the parts be made in generation of a matter like to that which maketh them in nutrition? If they be augmented by one kind of juice that after several changes, turneth at the length into flesh and bone… why should not the same juice, with the same progress… be converted at the first into flesh and bone though none be there formerly?”
By considering the embryo as a physical entity, fundamentally linked to the very same matter present in our food, Digby gave developmental biology a material basis it previously lacked. Indeed, most scholars at the time still sought explanations in Aristotle’s two-thousand-year-old framework of ineffable ‘causes’ and ‘humors.’
Digby’s work also spurred another scholar, his rather more staid colleague Nathaniel Highmore, to his own studies. Highmore’s cleverly titled 1651 History of Generation – Examining several opinions of divers authors, especially that of Sir Kenelm Digby… should be more well known, as it was very first to report observations of an embryo using a microscope. They were chicken embryos, of course.
Highmore extended Digby’s ideas on nutrition, going on to discuss “small indivisible… Atomes” and how they “fall to their proper places, and make up a Chick…” Now, these are not the atoms we know today, but rather an earlier conception whose history we needn’t delve into here. And of course Highmore and Digby weren’t the only ones studying embryos at the time. William Harvey is by far the most well-known embryologist of the day, but we can talk about him another day.
Suffice to say, Digby and Highmore’s chick studies were important, so let’s put them into context: To do so, cast your mind back to high school chemistry and Boyle’s Law. That Law was just one of Robert Boyle’s accomplishments, for he was a pillar of the Scientific Revolution. In fact, his book The Sceptical Chymist is generally considered to mark the dawn of modern chemistry, the science of how things are constituted. A friend to both Highmore and Digby, Boyle had read their work, and when his own magnum opus was published some ten years after theirs, Boyle noted a key implication of his new chemistry: to “teach us how a Chick is formed in the Egge.”
So, right there, at the very dawn of modern science, at the very moment we began to build a new conception of matter, the humble chicken was already helping to build a new conception of the embryo.
Digby and Highmore thus tied a crucial knot in the thread that connects Erica Hutchins’ work with chick embryos to Aristotle’s. Two hundred years after Digby and Highmore, Karl Ernst von Baer’s studies of chick embryos would mark the birth modern embryology in the 19th Century. A few decades after that, in the hands of Wilhelm His, the chick would give up the very first secrets of what we now call the neural crest. And of course, in the 20th Century, Nicole Le Dourain and Marianne Bronner, among others, would build the chick neural crest into a massively powerful paradigm for interrogating the mechanisms of embryonic development.
So, I told this story because I read Erica’s paper and she’s starting a lab with chick embryos, and I wanted to write about how the chicken basically did everything cool in #devbiol for like 3000 years. But I want to stress here that Erica’s not alone. I might just as easily have built this story around other new PIs using the chick for cutting-edge #devbiol. Amy Shyer’s physical/mechanical approach might remind Digby of his friend Descartes; Mike Piacentino’s work on lipid metabolism might get us closer to Digby’s nutritious “juice.”
So let’s be clear, the longest thread in the huge tapestry of #devbiol is still being spun from chick embryos. And, as Digby wrote, “by drawing the thread carefully along through your fingers, and staying at every knot to examine how it is tied; you see that this difficult progress of the generation of living creatures, is obvious enough to be comprehended.”
In the research paper by Nayelli Marsch-Martínez, Irepan Reyes-Olalde, Antonio Chalfun-Junior and colleagues, we report on the finding of a gene that appears to have been generated de novo, in a specific branch of the plant kingdom (Fig. 1). Some years ago, the idea of genes arising from non-genic sequences was thought to be highly unlikely, since genes were thought to arise from previously existing genes. This gene exquisitely modifies plant growth when overexpressed, causing twisted growth in many organs (Fig 1 or 2). Interestingly, even though this is a recent gene, its loss of function in the model plant Arabidopsis thaliana leads to developmental defects. There are very rare examples of new genes that influence development in such a clear way.
Figure 1. The TWISTED gene is only present in a branch of the plant kingdom. In Arabidopsis, it produces helicoidal growth when overexpressed, and the loss of its function affects development.
How did you get started on this research?
This research started very long ago. It lasted almost 20 years, with pauses. Nayelli had moved from Mexico to The Netherlands to build an activation tagging population, as part of her Ph.D. (Marsch-Martinez et al., 2002). Many beautiful and interesting mutants were obtained, and other groups came to look for cool phenotypes. The twisted (twt) mutant was discovered by Jurriaan Mes when he came to screen the population and found a plant with siliques growing as helices. Since then, many people have worked on the mutant, first trying to identify the gene that was causing such a curious phenotype. When Nayelli, together with Stefan de Folter, moved to Mexico to work at CINVESTAV-IPN, the mutant came along, and the quest continued there.
What was already known about the twisted gene?
Actually, there was nothing known. We started by isolating the flanking region of the activation tagging element that was causing the phenotype. At that moment, the TWISTED gene was not even annotated. This caused a lot of trouble, because at the beginning, we tried to recapitulate the phenotype by overexpressing other genes, but never got the phenotype. Many constructs and transformants went by and we did not have the gene that was causing the twisted phenotype.
When doing the research, did you have any particular result or eureka moment that has stuck with you?
Yes, we were happy with the results of the recapitulation experiments, and it was very cool to finally see the recapitulation of the phenotype with the small gene. Also during this period we found that when a silencing construct was introduced into the activation tagging mutant, its phenotype was suppressed, which was exciting.
Another interesting moment was when we finally realized and accepted that this gene was not a common gene, and that probably was present only in a group of plants. This was hard to believe some years ago. A third moment was when the Cas9-edited plants showed phenotypes. We were not expecting that the loss of function of a taxonomically restricted gene would affect development like that. We thought it would maybe be more involved in coping with environmental conditions rather than development itself.
And what about the flipside: any moments of frustration or despair?
The first recapitulation experiments that Antonio (who did the initial experiments) tried, did not produce the phenotype, and this was very disappointing. He did a lot of work overexpressing different genes, analyzing their expression with marker lines and so on, but all the genes he worked on were not responsible for the phenotype. Another difficult moment was when we did the first BLAST searches and did not find any homologous sequences. At that time, these searches would produce zero hits. When Irepan, who also worked on the identification and characterization of the gene, presented the lack of hits in his master seminar, half of his classmates in the auditorium would tell him he was wrong. They could not believe that there was a gene that would not have any homologous sequences in the database. In recent years, we found hits to sequences only from species that are very close to Arabidopsis, but there was nothing at the time when we had just identified the gene.
It was also difficult to obtain a loss-of-function mutant. We ordered T-DNA insertional lines, but they did not cause knock-outs. One, where the T-DNA insertion was located in the UTR, even slightly increased the expression of the gene. Moreover, the phenotypes of silencing lines were not conclusive. It wasn’t until the CRISPR-Cas9 technology was available that we could have a real knock-out.
Where will this story take the lab?
For the moment, the different labs that participated in this study are working on other genes and subjects. We are also focusing on other genes, but we are still working on a side project in collaboration with Luis Delaye, one of our coauthors, to study the evolution of the gene in a more detailed manner. Nevertheless, it would be great to use this gene later in the future to modify fruit shape!
What next for you/your lab after this paper?
We continue to study fruit development and organ development in general, trying to discover new genes that participate in these processes.
Reference:
Marsch-Martinez, N., Greco, R., van Arkel, G., Herrera-Estrella, L., Pereira, A., (2002), Activation Tagging using the En-I maize transposon system in Arabidopsis, Plant Physiology, 129:1544-1556. https://doi.org/10.1104/pp.003327
We recently announced that we will be working with three newly appointed the Node correspondents, who will be helping us to develop and write content for the Node in 2023. We caught up with each of them to chat about their research backgrounds and the topics that they’re excited to write about over the course of the coming year.
The final member of the correspondents team (which also includes Brent Foster and Alexandra Bisia) is Dina Mikimoto. Dina works as a Postdoctoral Researcher at the University of Tokyo in Japan. She has moved from the field of analytical chemistry into the field of tissue engineering which also involved her moving from Moscow to Tokyo. We discuss the challenges and opportunities that arose from this transition. Also, we talk about the importance of explaining her own work (and work within the wider tissue engineering field) in a clear and concise way – whether to friends or colleagues – and how joining the correspondents team can help her to achieve this goal.
Congratulations on being selected as one of our new the Node correspondents. How did you find out about the role, and why did you decide to apply for it?
I found out about this opportunity while browsing the Node website. During the last year, I’ve been doing quite some thinking about the things I like most about research. I concluded that it is writing papers, drawing schemes for these papers, and then trying to explain the findings in these papers in very simple terms. Actually, I find that many people – whether friends or colleagues – misunderstand what I’m working on which makes explaining my work in a clear and concise way even more important to me.
I was thus looking for ways to communicate my research in a more systematic way. So when I saw this opportunity on the Node, I thought it was a perfect fit. Many of the things that appear on the Node are very close to my heart (and research field!). In my role as the Node correspondent, I hope to surround myself with people who can help me further develop my communication style and help me express myself and my ideas clearly.
Have you done any science writing before, or will this be a new experience for you?
When I was a student in Moscow, I joined a science communication journal for which I wrote a few articles. I couldn’t really choose what to write about though – like one time I was asked to write about sustainable education, and I wasn’t even sure where to start. Of course, it was a really interesting and important topic, but I didn’t feel like I would be the right person to cover it. Instead, I’d rather write about something in which I’ve acquired some expertise and is closer to what I work on.
What is your current research focus? And how did you get into your current position?
I’m originally from Russia where the education system is geared towards mathematics and physics. Biology and chemistry receive less attention, though I was more attracted to these subjects straight away. Initially more to chemistry than biology as I really enjoyed the logical, systematic approach of it. But I was always torn between the two, explaining how I ended up in a PhD in biochemistry in which I studied enzymatic reactions that could be used to help diagnose certain neurodegenerative diseases.
While I was doing my PhD at the Moscow State University, I read a lot of literature about the diseases I was trying to detect with the enzyme-based biosensor I was working on. Rather than just the detection of diseases, I became more interested in work focused on preventing disease. I realised that biochemistry would not be ideally suited for me and I looked for more interdisciplinary fields. It’s how my interest shifted toward the tissue engineering field. Japan is at the forefront of tissue engineering and so I realised this might be the right place for me to go – I wanted to be at the centre of things.
So I did indeed go to Japan where my supervisor advised me to start another PhD, this time in tissue engineering. Since I finished my first PhD in Russia at the age of 25 – the time when most people in Japan start their PhD studies – I thought why not and decided to go for it. Since then, I have received my 2nd PhD and now I am trying to build a bridge between my two works.
So you ended up moving from Moscow to Tokyo – what was that like?
I had made some friends in Japan already, including my current husband. When I was doing my PhD in Moscow, a devastating earthquake hit Japan (in 2011). Japanese students at the Moscow State University organised many events to raise awareness of this disaster and I wanted to help in any way I could. I ended up befriending these students (who also studied Russian) and had already visited them a few times before my official move to Japan. It meant that when I moved, I didn’t feel alone at all. Still, it’s very difficult for foreigners to settle down in Japan. They’re very friendly, but there is a lot of difficult paperwork to complete (all in Japanese!).
I was lucky to have my friend, now husband, help me out with the paperwork. Not only this, but there are actually a lot of elderly people who actively help foreigners to settle in. When people retire in Japan, they look for a hobby: for some, this is to help foreigners. So these people know a lot about Japanese society, know nice places to visit (better even than most young people) and speak English really well. In short, they are a treasure of information and made me feel very welcome indeed. The academic atmosphere in Tokyo is also very welcoming and so I was well set up in Tokyo at arguably the epicentre of tissue engineering research.
Are you planning to write about tissue engineering for the Node? Or are you looking to branch out into other areas?
I would definitely like to write about tissue engineering first. It’s a very fluid research area with influences from many different fields of research. Just in my own lab alone, we have engineers, chemists, programmers, and biologists all working together. I think this mixture of expertise is one of the most exciting aspects of tissue engineering and I’d like to write about the origin of different ideas within this field.
I sometimes feel that tissue engineering is a bit like what the field of “alchemy” used to be: the field that wanted to turn metal into gold. Its goals are perhaps a bit too ambitious at times, but in pursuing ambitious goals many interesting and important observations are being made. Doubtless, the field of tissue engineering will evolve but in which direction is still unclear – which in itself is fascinating.
There are quite a lot of people who have strong feelings about tissue engineering and I’d definitely like to touch on some of the ethical considerations and questions within and surrounding the field. What could be interesting is to compare the regulations across different countries, as I know there is already quite a big difference between Japan and most European countries in terms of regulations.
What are you hoping to gain from the experience of being a the Node correspondent?
One of the things I’d really like to experience is what it is like to be a science writer. In the back of my mind, there is always this voice saying: “you really like to write, so maybe you should write more than you currently do. Maybe you should consider it as a possible career option.” Given my broad background, I do think this could indeed be a good way forward. Last year, when I had a bit more time on my hands, I started Tweeting for my lab, trying to explain the work we’re doing, posting funny videos about fibroblasts etc. I really loved it and look forward to doing more of this kind of work!
Finally, could you perhaps tell us something that people may not know about you? For example, what do you enjoy doing in your spare time?
I love knitting!
Here in Japan, only grannies are supposed to like knitting. But so do I, I guess. Nothing too complicated though, it needs to be relaxing. I mostly make scarfs which I have now given away to many friends and colleagues. They seem to really like them which makes me happy!
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