Robinow Syndrome is the best known of a set of genetic disorders that affect the growth and development of the skeletal system. Patients with these conditions have facial abnormalities, such as cleft palate, and develop short-limb dwarfism by around 18 months. Now, in a study published in Development, scientists from Nationwide Children’s Hospital in Ohio, USA, and the Van Andel Research Institute in Michigan, USA have shown the first successful correction of limb length in a mouse model of a very similar disorder known as FZD2-associated autosomal dominant Robinow Syndrome, providing hope for future therapies.
The forelimb (top) and hindlimb (bottom) of a mouse embryo, stained to reveal the bones (purple) and cartilage (blue). Image credit: Sanika Vaidya.
Although autosomal dominant Robinow Syndrome disorders are extremely rare (affecting around 50 families worldwide), they’re associated with genetic variations (mutations) in a group of genes that can be inherited from one parent or arise spontaneously, meaning diagnosis is not always trivial. Professor Rolf Stottmann who led the study said, “we began the project by studying the genomes of families with structural birth differences of the brain and face who had not yet received a genetic diagnosis. We identified that one of the initial families in this cohort had a mutation in the FZD2 gene.”
FZD2 is now known to be one of the known genes linked to autosomal dominant Robinow Syndrome. Like the other genes in this group, FZD2 makes a protein involved in sending signals that cells use to organise themselves into tissues. In their study, Professor Stottmann and colleagues used CRISPR/Cas9 genome-editing technology to induce mutations in a precise region of Fzd2, reproducing the specific types of mutations found in human patients. The researchers found that mice with these mutations had facial and skeletal malformations resembling those seen in the patients, including cleft palates and limbs less than half the normal size.
The researchers predicted that these types of Fzd2 mutations would disrupt signalling and hinder skeletal growth. To rescue the missing signals, the scientists intervened by treating pregnant mice with a drug that stimulates the signalling pathway. “This drug is an attractive option because we think we know how it works and previous work had shown that it could rescue cleft palates in a mouse model,” Professor Stottmann explained. Strikingly, they found that the pups exposed to the drug had significantly longer limbs than the untreated model mice.
The success of these experiments in mice suggests the drug could also be used as a therapeutic treatment in human patients. “The idea of treating the limb bones medically rather than surgically is a really important proof of principle, which we demonstrate in this study,” said Professor Stottmann, “we are very excited to test if this could work in the context of other genes associated with autosomal dominant Robinow Syndrome.”
Liegel, R.P., Michalski, M.N., Vaidya, S., Bitterman, E., Finnerty, E., Menke, C.A., Diegel, C.R., Zhong, Z.A., Williams, B.O., Stottmann, R.W. (2023). Successful therapeutic intervention in novel mouse models of Frizzled 2-associated congenital malformations. Development, 150, dev201038. doi:10.1242/dev.201038
In our February SciArt profile we feature Julie Gamart. In her illustrations, Julie seeks to combine the scientific topic with the personal preferences of the scientist(s) to create beautiful and playful artworks that communicate with her audience.
Where are you originally from and what do you work on now?
I was born in Saint-Martin-Boulogne, on the sea coast in the North of France. I stayed at the University of Lille (USTL, France) as a graduate student. As I wanted to work on genetics, I moved to Paris for the Master’s degree ‘Magistère Européen de Génétique’ where I had the opportunity to do a research internship at the University of New York (NYU Langone Health, USA) and then my master’s thesis in the laboratory of Professor Frédéric Relaix in the Institut of Myology in Paris. I was supervised by Dr Vanessa Ribes, and she gave me her passion for developmental genetics, working on the spinal cord development. I did my PhD in Basel in Switzerland in the Laboratory of Professor Rolf Zeller. I was using developmental genetics to decipher the roles of the BMP signalling pathway during the outgrowth of the limb bud. During my career, I have come to realise how a good illustration can improve scientific communication. Today, I draw for scientists and I like to translate a scientific message with an artistic angle.
Were you always going to be a scientist?
Not really. When I was a child my wishes were split between my desire to work on the art field, since I have this gift of drawing transmitted by my family, or my curiosity to understand how genetics works because my family has a hereditary disease. I finally chose the scientific path thinking that one day I would be able to reconnect with art.
Genetics & Cardiac Development This heart is used as a background on the website of the lab of Professor Marco Osterwalder (DBMR, Bern, Switzerland) to illustrate the research topic about Genetics & Cardiac Development. The drawing style is inspired by metal music. Link: https://www.osterwalderlab.com/
And what about art – have you always enjoyed it?
Yes, I managed to reconnect with art. After my PhD, I started to draw again, making artistic and scientific illustrations to communicate my research. I got a lot of good feedback, so I started to make illustrations and figures for my friends. Now I enjoy working with scientists from different fields to build unique illustrations that translate the scientific topic and reflect the tastes and preferences of researchers.
The Faces of a Brain Cancer Cell This illustration was submitted for the journal cover for the publication Parmigiani, et al. (2022). Based on an idea of a famous movie, it shows the two faces of a brain cancer cell interacting with immune cells: the one with the Notch pathway, being attacked by T cells (T shaped ships) and the one without Notch, recruiting immunosuppressive macrophages (M shaped ships).
What or who are your most important artistic influences?
I have no specific artistic influences. I learned to draw with several techniques when I was young, thanks to Jean-Francis Mulier’s classes (in Seclin in the North of France) that I followed from 10 to 16 years old. My main influence comes from my mother, Christine Gamart, and my aunt, Catherine Gamart, who support me in my decisions and give me very constructive advice and criticism. They draw wonderfully, their expert eye is essential for me.
How do you make your art?
The most important thing for me is the communication with the researchers. The illustration is a construction that we make together: it must translate a scientific message in a playful way and correspond to the personality of the scientist(s) to reflect his or her tastes and preferences. After that, I begin by choosing a drawing technique (acrylic, watercolour, charcoal, pastels, pencil). The technique will help to define the style of the drawing. Depending on the request, I use the computer to create a digital montage of the different drawings. For other realizations, I make the figures directly on the computer. I share my work on the networks (Facebook, Instagram, LinkedIn and Twitter) and my website.
The Mouse Heart Development This figure was used for the ‘Night of Research 2022’ organised by the University of Bern, where the general public was invited to meet scientists to talk about their research. The figure explains how the heart develops in mouse embryos during the 20 day of gestation period.
Does your art influence your science at all, or are they separate worlds?
Both worlds are linked: I adapt and use art as a tool to communicate, to popularise and share a scientific message.
You recently created the visual identity for the Franco-Japanese, New Frontiers in Developmental Biology meeting. Can you tell us a little about your brief and how you can up with the concept?
It was a great adventure to participate in this congress. The SFBD committee came to me and asked me to create a poster mixing developmental biology, Japan and the organising city, Strasbourg. The idea of creating the skyline of Strasbourg made of embryos from different species came quite quickly, in agreement with the team. To bring more poetry and softness, I proposed making the drawings using watercolour. The sun and the dominance of light pink colour also represents Japan and the flower of the Japanese cherry tree. From the style of the poster, we have created derivatives for different media (indication panels, presentation slides, name tag booklets) and some illustrations were used to create the website of the meeting. I also did the illustrations for the developmental biology games as part of the outreach programme that was running alongside the meeting. I really enjoyed adapting the drawing to a childlike style to explain developmental biology to little ones.
The 3rd Franco-Japanese Developmental Biology Meeting Poster of the 3rd Franco-Japanese Developmental Biology Meeting. It shows developmental biology, Japan and the city of Strasbourg in an original and artistic way
What are you thinking of working on next?
I hope it is the beginning of a big adventure. I would like to help many scientists communicate their research and make a difference with illustrations that reflect their personality and transmit a scientific knowledge in a creative and playful way. I will soon be organizing a scientific illustration workshop for a laboratory’s anniversary in Paris. I hope this event will be a success, and will add another string to my bow to share my work and initiate new collaborations. In the future, I would like to adapt scientific illustration to different events and different media to allow a better popularisation of science and share its beauty with a large and diverse audience..
Thanks to Julie 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!)
Extreme self-confidence is found, but not warranted for the most part, for those who are objecting to science. But it’s also found amongst those who are highly in favour of science. And the neutrals are: they know they don’t know.
Prof Laurence Hurst
In the latest episode of the Genetics Unzipped podcast, we’re sharing the results of a large survey asking the UK public what their opinions are, what they know, or more importantly, what they think they know about genetics and what that means for society.
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
On Wednesday 25 January, Development hosted three talks on the topic of theoretical and computational modelling of development and stem cells.
Below you’ll find each of the talks and Q&As hosted by our Associate Editor, Paul François (who recently moved to the University of Montreal from McGill University).
Simon Freedman (Senior Bioinformatics Scientist at Illumina presenting Postdoctoral work from Madhav Mani‘s group at Northwestern University) ‘A dynamical systems approach to cell fate decisions’
Mindy Liu Perkins (Postdoctoral Fellow in Justin Crocker‘s lab at EMBL presenting work from Hernan Garcia‘s lab) ‘A bistable autoregulatory module in the developing embryo commits cells to binary fates’
We would like to ask the ERC council to consider removing the ‘academic age limits’ as an eligibility criterion for applying for ERC Starting and Consolidator grants. The current “post 7 years” and “post 12 years” after PhD limits are extremely limiting and not in line with current timelines of research, especially in the Life Sciences. There are multiple reasons to ask for this (see examples below), but the main consensus is that such age limits select against social, economic, gender, ethnic and scientific diversity as it promotes people from privileged backgrounds, with straight forward and fast career paths, who are not necessarily the best scientists and mentors of future scientists. Scientific career paths are diverse, so putting one set of absolute time frames on different fields and different personal circumstances does not make sense. Experiments in animal models take much longer than theory. There may be delays due to different caring duties (of which child-birth is only one), illness, moving countries, changing fields, etc. With the current ‘age limits’, especially in countries where the ERC grants are the main source of large funding, once you ‘miss the boat’, you will never catch up, and your scientific career is severely impacted or prematurely ended. Should we be selecting scientific excellence based on speed, or quality?
We understand that to try to limit proposals submitted, and to have categories /cut offs to reflect career stage, there should be some ‘time-based’ criteria. Many countries, such as the UK, have removed these ‘absolute post PhD academic age limits’ on grants, and has thrived on new systems based on ‘new’, ‘mid’, or ‘senior’ investigators. If the ERC insists on having some time limits, we propose that a system such as this will be more inclusive:
– Starting Grant: up to 5 years since independence (defined as starting own group, faculty position, able to supervise PhD students independently, etc).
– Consolidator Grant: up to 12 years since independence.
– Advanced Grant: more than 12 years since independence. (the current extensions to the above due to child birth, illness, etc, should still be applied).
At the end of 2022 we launched our Node correspondent programme. We were looking for three researchers to help us develop and write content for the Node in 2023. The quality of the applications was extremely high, which made choosing our final three very difficult! We are delighted to announce that we have appointed Alex Bisia, Brent Foster and Dina Myasnikova as our correspondents for 2023. Our correspondents will benefit from a programme of writing groups, webinars and workshops coordinated by the in-house team at The Company of Biologists and will produce approximately six blog posts over the course of the year. We introduce our correspondents briefly below – stay tuned for longer interviews!
Alex is completing her DPhil (PhD) at the University of Oxford with Elizabeth Robertson, studying the role of Eomesodermin, a T-box transcription factor, in the trophoblast and definitive endoderm in the early mouse embryo. Alex has a strong interest in science communication; she won the BSCB writing competition in 2020 and has contributed articles to her departmental website. Look out for Alex’s posts on non-model organisms, science history and contributions of developmental and stem cell biology in medicine.
Brent is a technician at the University of Florida, working at the Whitney Laboratory for Marine Bioscience. Brent uses comb jellies and other marine invertebrates to study the evolutionary origin of nervous systems. He has previously written feature articles for his local newspaper, Society for Integrative and Comparative Biology (SICB) blog posts, and has attended several science writing workshops. Brent has a keen interest in non-model organisms and tool and technique development and will post on these topics.
Dina is a Project Researcher at the Biohydrid System Laboratory at the University of Tokyo, where she is working on developing an organ-on-a-chip model of peripheral diabetic neuropathy. Having worked in an interdisciplinary team, she is keen to improve communication between scientists from different research backgrounds. As well as exploring interdisciplinary research, Dina is passionate about helping women in science and will post on this topic.
Welcome to our monthly trawl for developmental and stem cell biology (and related) preprints. Congratulations to all the researchers who kicked off 2023 by preprinting their research.
The preprints this month are hosted on bioRxiv – use these links to get to the section you want.
Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies a preeclampsia-like gene signature Nataly Stylianou, Ismail Sebina, Nicholas Matigian, James Monkman, Hadeel Doehler, Joan Röhl, Mark Allenby, Andy Nam, Liuliu Pan, Anja Rockstroh, Habib Sadeghirad, Kimberly Chung, Thais Sobanski, Ken O’Byrne, Patricia Zadorosnei Rebutini, Cleber Machado-Souza, Emanuele Therezinha Schueda Stonoga, Majid E Warkiani, Carlos Salomon, Kirsty Short, Lana McClements, Lucia de Noronha, Ruby Huang, Gabrielle T. Belz, Fernando Souza-Fonseca-Guimaraes, Vicki Clifton, Arutha Kulasinghe
Nr5a2 is essential for morula development Nicola Festuccia, Sandrine Vandormael-Pournin, Almira Chervova, Anna Geiselman, Francina Langa-Vives, Rémi-Xavier Coux, Inma Gonzalez, Michel Cohen-Tannoudji, Pablo Navarro
Dominant-negative mutations in CBX1 cause a neurodevelopmental disorder Yukiko Kuroda, Aiko Iwata-Otsubo, Kerith-Rae Dias, Suzanna E.L. Temple, Koji Nagao, Lachlan De Hayr, Ying Zhu, Shin-Ya Isobe, Gohei Nishibuchi, Sarah K Fiordaliso, Yuki Fujita, Alyssa L. Rippert, Samuel W Baker, Marco L. Leung, Daniel C. Koboldt, Adele Harman, Beth A. Keena, Izumi Kazama, Gopinath Musuwadi Subramanian, Kandamurugu Manickam, Betsy Schmalz, Maeson Latsko, Elaine H Zackai, Matt Edwards, Carey-Anne Evans, Matthew C. Dulik, Michael F. Buckley, Toshihide Yamashita, W. Timothy O’Brien, Robert J. Harvey, Chikashi Obuse, Tony Roscioli, Kosuke Izumi
Establishment of cell transcriptional identity during seed germination Lim Chee Liew, Yue You, Marina Oliva, Marta Peirats-Llobet, Sophia Ng, Muluneh Tamiru-Oli, Oliver Berkowitz, Uyen Vu Thuy Hong, Asha Haslem, Tim Stuart, Matthew E. Ritchie, George W. Bassel, Ryan Lister, James Whelan, Quentin Gouil, Mathew G. Lewsey
Generation of human alveolar epithelial type I cells from pluripotent stem cells Claire L Burgess, Jessie Huang, Pushpinder Bawa, Konstantinos-Dionysios Alysandratos, Kasey Minakin, Michael P Morley, Apoorva Babu, Carlos Villacorta-Martin, Anne Hinds, Bibek R Thapa, Feiya Wang, Adeline M Matschulat, Edward E Morrisey, Xaralabos Varelas, Darrell N Kotton
Epithelioids: Self-sustaining 3D epithelial cultures to study long-term processes Albert Herms, David Fernandez-Antoran, Maria P. Alcolea, Argyro Kalogeropoulou, Ujjwal Banerjee, Gabriel Piedrafita, Emilie Abby, Jose Antonio Valverde-Lopez, Inês S. Ferreira, Stefan C. Dentro, Swee Hoe Ong, Bartomeu Colom, Kasumi Murai, Charlotte King, Krishnaa Mahbubani, Kourosh Saeb-Parsy, Alan R Lowe, Moritz Gerstung, Philip H Jones
Emergent dynamics of adult stem cell lineages from single nucleus and single cell RNA-Seq of Drosophila testes Amelie A. Raz, Gabriela S. Vida, Sarah R. Stern, Sharvani Mahadevaraju, Jaclyn M. Fingerhut, Jennifer M. Viveiros, Soumitra Pal, Jasmine R. Grey, Mara R. Grace, Cameron W. Berry, Hongjie Li, Jasper Janssens, Wouter Saelens, Zhantao Shao, Chun Hu, Yukiko M. Yamashita, Teresa M. Przytycka, Brian Oliver, Julie A. Brill, Henry M. Krause, Erika L. Matunis, Helen White-Cooper, Stephen DiNardo, Margaret T. Fuller
Yesterday was my last official day as the Community Manager of the Node, and I wanted to take this opportunity to thank all the Node community for being so welcoming over the last 18 months. I’ll still be moonlighting on the Node, alongside preLights Community Manager Reinier Prosée, until we have the new Community Manager in place. If you have any questions, comments and feedback, you can still contact us at thenode@biologists.com. It’s lucky that I get to hang around for a while longer, as we have been working on a couple of new projects that we hope to share with you in the next month. Watch this space!
One of the projects that we are working on is a collaboration between the Node and FocalPlane. FocalPlane will be my new home as I have moved across to join the Journal of Cell Science team as FocalPlane Community Manager. If you use microscopy as part of your work, or would like to get started, I recommend checking out our website! Like the Node, FocalPlane is driven by the community, so if you have any feedback, suggestions or comments please get in touch at focalplane@biologists.com or helen.zenner@biologists.com. If you would like to contribute to the site with a blog post, event listing, or job advert, you can register and request permission to write, and once approved you’ll be ready to go.
Thanks again for all the fun times on the Node. I’ve had the opportunity to interact with some amazing people, not least the wonderful team at Development – Alex, who puts up with all my ‘stupid’ questions (not sure this is going to stop), Seema, who helped me so much when I started, and Katherine, who is the most excellent manager! I’m now excited to try and bring some of ‘the Node spirit’ to FocalPlane and hope to see you there.
At the Joint Society for Developmental Biology (SDB) – Pan-American Society for Evolutionary Developmental Biology Meeting in 2022, I spoke to Christopher Wright, the winner of the 2022 SDB Victor Hamburger Outstanding Educator Prize. You can read the interview in Development, but Chris shared some stories that we couldn’t squeeze in, so with his permission I have reproduced a couple of examples here. I selected these stories as they show the fun side of doing science and the excitement for biology that Chris expressed throughout our interview.
Science on a whim
“When I was in Eddy de Robertis’ lab for my postdoc, we decided to start probing the organizer region – the Spemann-Mangold organizer – for homeobox genes. We did this on a whim when Eddy went on vacation, and when he came back several people in the lab were running around clearly excited running old-school “high-throughput” DNA sequencing by hand. We told Eddy what we’d done and he was somewhat shocked. But, in the end, organizer molecules were what set his lab moving forward for the next 10 or 15 years. Out of that work came goosecoid. A huge amount of work went on after I had left, but finding goosecoid and naming it, based on part of its homeodomain sequence resembling the fruit fly gene gooseberry and the other part bicoid, was great. We decided that ‘bicberry’ sounded wrong but goosecoid stuck. It felt like we had just joined the Drosophila community and could name things crazily! There was an important lesson in this situation: when working with postdocs, the challenge for the PI is to understand that there are often things that are done outside of the PI’s undoubted own brilliance. Great postdocs should be semi-independent almost straightaway. You want them to cause (almost) paroxysmal change in the lab. I think Eddy learnt that. And Eddy was phenomenal to just talk to about science, he was always asking, “what do you think this means?” I remember looking down the microscope together, at the first Xenopus nuclei ever labelled with antibodies I’d made to the homeodomain proteins. He jerked me up from the microscope and gave me a huge hug!”
Seeing is believing
“It is wonderful to look down the microscope at new findings. One fun time was when Yoshiya Kawaguchi, a terrific Japanese postdoc with me, did an experiment that would be the first time that lineage tracing was combined with a gene knockout in the endoderm. He took the pancreas master transcriptional regulator called Ptf1A and hooked it up to Cre. The Cre replaced the protein, so was essentially a knock-in as a knockout, and we had a ROSA26-lacZ reporter in there too. One day he came bowling into my office and said, “Chris, Chris, Chris, you have to come right now and look at this embryo (which had been stained with X-gal overnight). The mutant is amazing”. And I said, “yep, okay, I’m coming right now. I’m really excited. Let me just tell you what I think you have found, I bet you found that all the cells that were going to become pancreas have now become duodenum”. He was shocked, asking “how can you know that?” I said, “don’t let that disturb you. Let’s go and look together.” As soon as I looked down the microscope, I knew this was an important result and we were so excited. It’s a memory that sticks with me, seeing that result for the first time!
Another result that really stuck with me was when we got involved in cloning Nodal, cobbling it together using various parts of the mouse gene, and isolating the frog orthologs. We injected the mRNA into Xenopus embryos and when we came back the next day, well – they had made notochord everywhere. This started our move away from homeobox genes. Left-Right asymmetry patterns came up from our Nodal work early on. This time I absolutely couldn’t believe the result to start with and I told my postdoc (the wonderful Karuna Sampath) that the pattern must be due to the side the embryos were lying down, having had some horrible glass reaction. She very kindly said “No, no, it’s all on the left-hand side of the embryo irrespective of which side they were lying”. Again, off we charged to look down the microscope straight away!
Overall, I have so many exciting moments in my career, and I feel very privileged and fortunate to have been born at the right time, landed in the right place and then to have done at least some of the right experiments!”
Thanks to everyone who interacted with the Node in 2022, it been another fantastic year for the site. We have a few new initiatives that we’ll be announcing soon, but first let us look back on 2022!
What are you looking at…
>400,000 total page views
18,483 views of our jobs board
4,992 view of our event calendar
What’s being posted…
226 blog posts, including 7 SciArt profiles, 7 Featured resources, 12 behind the paper stories and 12 preprint lists
At number two on our list was the livestream from our Development meeting ‘From Stem Cells to Human Development. Setting this up was a little nerve wracking and it was fantastic to see so many people tuning in live and viewing the recording, which featured talks from Sarah Teichmann and Sergiu Pasca and a panel discussion on ‘Technical, ethical and legal challenges of studying early human development’.
The third most read post started on a whim, with Alex Eve converting his popular #wordcountchop tweetorial into a blog post. If you have written a tweetorial on a topic relevant to developmental and stem cell biologists and want to give it a more permanent home, do considering sharing it as a blog post on the Node
Voting for your favourite Development cover comes in as our 4th most read post. Everyone loves a competition, and we had a worthy winner with the Issue 21, the mouse lung lobe from Prashant Chandrasekaran, Nicholas Negretti, Aravind Sivakumar, Jennifer Sucre, David Frank and colleagues. Keep your eyes out for our next competition, which is coming soon!
Joachim Goedhart’s Protocols for data visualization came in at number five. In this post, Joachim shared an update on his book, which brings aims to lower the barrier for using R and the ggplot2 package for data visualization. Joachim’s post on Data Visualization with Flying Colours, published in 2019, was again our most read post with a massive 49,405 views!
We would love to hear feedback and suggestions on how we can make the Node better in 2023. You can contact us using our contact form and at thenode@biologists.com. We are always happy to discuss ideas, comment on drafts, or help with website gremlins. Finally, remember the Node is your site and, once registered, you can post freely.
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