On 21 June 2023, Development hosted a webinar featuring talks on the topic of growth and morphogenesis from three early career researchers, chaired by Development’s Editor-in-Chief, James Briscoe. Below are the recordings of the talks.
Patricio Pérez-Henríquez (University of California, Riverside)
Talk and Q&A by Patricio Pérez-Henríquez
Stefania Tavano (MedUni Vienna)
Talk and Q&A by Stefania Tavano
Stefan Harmansa (IBDM and Turing Center for Living Systems)
Talk and Q&A by Stefan Harmansa (No Ratings Yet) Loading...
Looking forward to welcome you to our EMBO Workshop – Developmental metabolism: flows of energy, matter, and information
Recent work revealed the intricate relationship between energy flux, spatial and temporal control of metabolites, the environment, and embryogenesis🤯. #EMBODevMet
Hydrozoan cnidarians have a population of stem cells, known as i-cells. The developmental potential of only one other hydrozoan i-cell has been described before this paper. Hydra‘s i-cells can give rise to the neuroglandular lineage and to germ cells. Their ectodermal and endodermal epithelial cells are self-renewing, constituting separate lineages. i-cells multipotent but not pluripotent (Bosch & David, 1987).
In terms of Hydractinia, it was established that a population of stem cells (known as i-cells) were able to give rise to every single lineage (Müller, et al., 2004). This showed that as a population, i-cells can give rise to the somatic and germ cell lineages. The potential of a single i-cell, however, was still unknown. Either i-cells had their own distinct lineage restricted sub-populations or they were pluripotent, and one i-cell could give rise to all cell types.
The aim of my research was to transplant a single i-cell and observe it in vivo. For this purpose, we had an extremely useful fluorescent reporter animal at our disposal. This animal had two fluorescent transgenes, the first transgene was Piwi1- driven GFP which is expressed in only i-cells and germ cells. It is downregulated in differentiated cells. The other transgene was Beta-tubulin- driven mScarlet. This transgene is expressed by all differentiated cells but not i-cells. This allowed us to identify i-cells by their GFP expression and lack of mScarlet expression and identify the i-cells progeny by their mScarlet expression and dim GFP fluorescence due to the half-life of the GFP. The aim of the project was to transplant a single GFP positive i-cell into a wild type recipient and identify the resulting progeny that would be identifiable by their mScarlet expression.
Bottlenecks on bottlenecks
Transplanting a single cell was my first objective when I started this project as a 1st year PhD student. I figured that it should take me 3-4 months maximum to get it sorted, optimised and then I could press on with the actual experiments and start generating some (hopefully decent) data. I began by looking at what single cell transplantations had been performed before in comparable models and hoped that it would be just as successful in Hydractinia.
Firstly, I tried incorporation of a cell via aggregation. This is something that was established in Hydra (Murphy & David, 1977). It required dissociation of full Hydractinia polyps. I could then identify a single i-cell by its GFP fluorescence and its lack of mScarlet fluorescence. This would then be picked up by a needle attached to a micro-injector and ejected into a tube full of dissociated wild type cells. These would then be centrifuged into an aggregate and cultured till, ideally, a polyp with a single transplanted i-cell would be established. Turns out, betting on a single cell surviving aspiration and/or centrifugation is a long shot. In meetings with my PI, Uri, I frustratedly referred to it as “a bottleneck on a bottleneck”.
After, countless amounts of failed transplantations via aggregation I was reinspired by the planarian community’s favourite method of single cell transplantation: direct injection into the animal (Wagner, et al., 2011). Perhaps by directly delivering a single cell I could finally cross off my first objective. This required a steady hand to ensure you didn’t overshoot the piercing of the epidermis and inject a cell into the gastric cavity. Unfortunately, after injecting into adult polyps and larvae from all angles I realised that this method wasn’t going to be feasible either. I was just not seeing any i-cell engraftment. It may have been a combination of mechanical issues on my part, maybe unhappy cells or also Hydractinia having a much more confined stem cell niche area than planarians do. Ultimately, we never found out why. We just knew it wasn’t a way forward to achieve our aims. At this point, I was almost 2 years into my PhD and that first objective was still not completed. The pressure was mounting, and I started considering alternative projects in the worst-case scenario. Whatever came next would be my last attempt at getting this project off the ground.
Keeping it in the niche
Finally, we had our own form of a eureka moment. We had been dissociating the animals to isolate one cell (like the planarian and Hydra communities had previously done) but we had overlooked something major and wonderful about Hydractinia. We had overlooked what sets them apart from both Hydra and planarians. Hydractinia is a colonial animal that can fuse and swap cells with a histocompatible relative via stolonal networks. I had been working to establish a method of transplanting cells when our model already had one itself. We could keep our i-cells within their own niche! I just had to find a way to effectively leverage it to my aims.
This began with me setting up Hydractinia “neighbourhoods”: a donor colony settled next to a recipient colony. The donor colony would grow and then fuse with the recipient by extended stolons and I could patiently observe i-cells migrating into the recipient tissue, waiting for a perfect moment to strike and isolate one cell (Figure 1). I had noticed that when the colonies were fed less, they were more likely to grow long branches of stolons rather than extending their mat. A long branch was preferable as it meant the i-cells could be transplanted “in single file” rather than like an encroaching army that was more unpredictable and difficult to follow a single cell. After numerous fusions of donor and recipient I isolated a single donor i-cell in a piece of recipient stolon tissue. The next day there were two i-cells. Then four. Then there were mScarlet expressing somatic cells AND i-cells. My transplanted cell was proliferating and differentiating. This new chimeric piece of stolon grew into a small colony with both wild type cells and cells derived from the one i-cell. Extraordinarily relieved, I checked off that first objective.
At the early stages there was a split between recipient and donor derived cells in the colony. To ensure that the donor cells were not outcompeted I performed “selective pruning”. This involved excising large portions of tissue that had only/mainly wild type recipient cells. This gave us a lot of peace of mind as we were more confident that the donor cells wouldn’t be outcompeted before they had developed sexual polyps.
Figure 1: Colony grafting via parabiosis. A wild-type colony is positioned close to a transgenic fluorescent colony. Fusion between the histocompatible relatives allows i-cells to move from one colony to the other. A small section of wild-type stolon with a single donor fluorescent i-cell is isolated by excising the surrounding donor and recipient tissues.(Varley, et al., 2023)
When the animal was sexually mature, we were excited to see sexual polyps that were male (from the recipient) but also fluorescent and female (from the donor). Some sexual polyps were even both. These donor derived GFP+ and mScarlet+ oocytes were able to be fertilised and gave rise to a new primary polyp that inherited the transgenes from the single donor i-cell (Figure 2). From this we knew that one i-cell can contribute to the next generation of Hydractinia.
Using live confocal microscopy on polyps cut from the colony, we were able to identify mScarlet+ neurons, epithelial cells, nematocytes and i-cells by their characteristic morphologies. Gland cells, however, were more difficult to identify. We didn’t have any antibodies that could identify them and even by morphology they often look like more vesicular epithelial cells. To address this, we had to look at it from a different perspective. At this later stage of the colony, we were able to confirm by flow cytometry that all cells present were transgenic and there were no recipient cells remaining. This meant that all cells, including gland cells, came from the single donor i-cell. This was the ultimate proof of pluripotency for us. There was not a single cell in the animal that one i-cell did not give rise to.
Don’t doubt your model
In humans, pluripotency occurs for a brief snippet of time pre-gastrulation. This paper established that Hydractinia stem cells are pluripotent for the full extent of their life. When starting, I didn’t expect for one single cell to be as globally influential as it was. In retrospect, I should have never doubted our model and its ability to impress.
Figure 2: Donor derived oocyte and germ cells (green) in a chimeric sexual polyp (Varley, et al., 2023)
References
Bosch, T. & David, C., 1987. Stem cells of Hydra magnipapillata can differentiate into somatic cells and germ line cells. Developmental Biology, pp. 182-191.
Müller, W. A., Teo, R. & Frank, U., 2004. Totipotent migratory stem cells in a hydroid. Developmental Biology, Volume 275, pp. 215-224.
Murphy, S. & David, C. N., 1977. Characterisation of interstitial stem cells in hydra by cloning. Developmental Biology, 58(2), pp. 372-383.
Varley, Á. et al., 2023. Pluripotent, germ cell competent adult stem cells underlie cnidarian regenerative ability and clonal growth. Current Biology, 33(10), pp. 1883-1892.
Wagner, D. E., Wang, I. E. & Reddien, P. W., 2011. Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science, 332(6031), pp. 811-816.
If you have been on Twitter or read the news recently, you have probably seen this Guardian article on stem cell-based human embryo models, or one of the other pieces of news coverage. This sparked some debate over how scientific data should be covered in the media. Should data without a preprint or paper be reported in the news? How should scientists talk about their results with journalists?
Following the Guardian article, the Zernicka-Goetz group and Hanna Group each released a preprint on post-implantation embryo models:
In light on the fast-developing field of embryo models, the scientific community is acting to produce a governance framework for research involving stem cell-based human embryo models. This includes a project recently launched by the University of Cambridge.
Stem cell-based embryo models could help our understanding of the problems that can affect early pregnancies.
But their regulation is a grey area. That's why @Cam_Repro has launched a project to develop a governance framework for this research in the UK 👇
— Cambridge University (@Cambridge_Uni) June 16, 2023
The ISSCR released their Standards for Human Stem Cell Use in Research, which “identifies quality standards and outlines basic core principles for the laboratory use of both tissue and pluripotent human stem cells and the in vitro model systems that rely on them.” This document also includes guidelines on best practice for reporting on studies using human stem cell systems.
The #ISSCR wants to better understand how LGBTQ+ scientists feel included in their professional societies, workplaces, & the broader community. We need your voice to create a more inclusive scientific community – take a moment to share your experiences 👉 https://t.co/CozpyiqzSipic.twitter.com/QfhZKMO5lS
And finally, have you ever heard of the police being called to a scientific conference because the conference hall was overcrowded? This happened at ISSCR2023.
This morning, a concurrent session exceeded fire code capacity and the building security ushered out non-seated attendees. They did this for a fire-safety reason, but in a way that was uncomfortable to involved attendees and somewhat disruptive to the session.
Police just interrupted a wonderful talk by Jing Qu on endogenous retroviruses and senescence to kick people out of the seminar room, due to it being over capacity :( #ISSCR2023
If you can’t attend the European Developmental Biology Congress in person this September, why not organise a local Watch Party?
Excitement is ramping up for the European Developmental Biology Congress which will take place 25-28th September this year. This will be a celebratory meeting distributed across three beautiful locations: Oxford, Paris and Barcelona, packed with exciting science, social events, medal talks and even chances to try Tai Chi, experience embryology-inspired Virtual Reality art and go punting with your fellow developmental biologists. You can read more about our plans here and you can check out the programme and register here.
For anyone who can’t travel to attend the meeting in person, there will be the option to watch talks online. But, we know that watching a conference remotely can sometimes feel a little lonely, with no one to discuss the talks with over a delicious conference coffee.
So…. why not plan an #EDBCWatchParty?
“Our lab organised an outdoor watch party in my garden for the 2021 hybrid BSDB Spring Meeting and it was great. I’d definitely do something like that again”
Kyra Campbell, University of Sheffield
“We hope to gather together Developmental Biologists from across Edinburgh to watch EDBC2023 in a university seminar room, perhaps with a local poster session. We will encourage people to bring home bakes so we might even include a Great Developmental Biology Bake Off competition!”
Tamina Lebek and Guillaume Blin, University of Edinburgh
“Our lab are excited about the talks at EDBC, but some of us can’t make it in person so we’re very keen on the idea of coming together to watch the talks online. We’ll spread the word around Cambridge for any other developmental biologists who’d like to join us”
Ben Steventon, University of Cambridge
If you are thinking of giving this a go, we’d love to hear about it so please feel free to drop us a line at meetings@bsdb.org or post on twitter or mastodon with the hashtag #EDBCWatchParty
The lab is in the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in the lovely Dresden (Germany).
Research summary
Mammals evolved divergent architectures of placenta to receive nourishment from the mother during embryogenesis. In our lab, we seek to understand how the uterine microenvironment shapes the fetal-placental interface of various animals, by using early embryos and placental organoids. Our ultimate goal is to investigate how complex and diverse structures emerge to achieve similar function.
Gerri lab members
Lab roll call
Michi: lab technician. I like to help in any situations and projects. Also, I like to work on my own little project, which is focused on discovering similarities and differences in early embryonic development of different species of mammalian pre-implantation embryos.
Johanna: PhD student. I work on the role of oxygen sensing mechanisms during early human placenta development.
Ornella: master student. I am investigating the impact of specific genetic mutation on human trophoblast stem cell differentiation and trophoblast organoid self-organization.
Weiwei: bachelor student. My project is focused on testing different live imaging approaches on 2D and 3D culturing systems.
Favourite technique, and why?
Claudia: My favourite approach in studying biology is imaging. I am fond of everything that allows us to visualize biological processes. It is in this way that we can describe new phenomena and decipher how biology works. Analysis of both live and fixed samples, for example using immunofluorescence or transgenic lines, accompanied by microscopy at different resolutions can allow us to look at biological samples at different scales, from intracellular tiny structures to multicellular complex tissues.
Apart from your own research, what are you most excited about in developmental and stem cell biology?
Claudia: Biological processes require a complex coordination of genetic, molecular and physical events in space and time. Several physical principles have helped understanding developmental processes in a more unified way. I am always impressed when reading multidisciplinary papers where experimentalists and theorists work together to identify emerging principles of the living matter.
This is why I have decided to join the MPI-CBG and the Dresden campus in general, where scientists across disciplines, biology and physics, actively work together. I hope with time to develop collaborations into this direction.
How do you approach managing your group and all the different tasks required in your job?
Claudia: We are a young lab, so I believe that at this stage it is important for me to be focused on the science and to be there for the lab members. I am still active in the lab and I try to be available to answer queries and discuss issues when the team members require to do so. In addition to institute seminars and conferences, I try to organize opportunities for the team to interact with other labs working with similar and different topics (e.g. lab retreat with Huch, Veenvliet and Toth-Petroczy Labs, but also joint lab meetings with Rodenfels Lab).
In general, to manage all the tasks required for this job, I try to plan my goals monthly, weekly and daily.
I am still learning and when in doubts I ask advice to other young group leaders and mentors.
What is the best thing about where you work?
Claudia: I have experience in other institutes, bigger and smaller than the MPI-CBG. I think the MPI-CBG is great in many aspects. MPI-CBG is an internationally renowned institute and that is why many great scientists from around the world come here to give talks. Also, the MPI-CBG is big enough to have diversity in terms of science and people, but also it has the right size to allow people to interact after seminars, or in the canteen. This really helps to create a tight community, where newcomers are welcome and can easily integrate into the institute.
We have also great excellent facilities helping us in our daily routine (e.g. organoid stem cell facility) or in developing new tools (e.g. genome engineering facility or technology development studio).
Michi: I like studying the develop of the placenta, because we discover unique aspects of developmental biology. I also really like the institute with its great facilities and the great international people working here. Also, there are small things, like the smell of coffee when you enter the building. All these reasons make me happy to come to work!
Johanna: I really like the way service is provided by all the facilities, and the sense of community. People of the lab and general from the institute are always very happy to help and support me with my projects.
Ornella: In my opinion, what makes the Gerri Lab truly exceptional is the continual support and guidance you get from everyone. We all have different backgrounds and personalities, but we have a great balance that makes the lab a fun and enjoyable place to be.
The Institute’s greatest aspect is the tight-knit community, where we all come together. Thanks to the international and interdisciplinary environment, there are abundant opportunities for personal growth and learning. Being exposed to internationally renowned researchers adds immense value to my experience. Plus, I particularly enjoy the social events, where we can relax and have a good time.
Weiwei: I really like the lab environment, everyone is very helpful, caring and patient. There are seminars to follow and many other activities, also a weekly get-together.
What’s there to do outside of the lab?
Claudia: Dresden is a great city to live in! I find that there are things for every taste. There is Altstadt, where you can go to visit museums and learn more about history. There are residential areas with amazing parks, where is great to spend time with the family. There is Neustadt, which is the vibrant and young part of the city. There is also amazing nature nearby.
Michi: I think Dresden is a great city with many things to do. Most of the city rivers are folded in concrete but we have the Elbe-meadows where you can bike, run, walk, having a picnic or even skiing in winter. In summer there is an outside theatre next to the river with an amazing view on Dresdens historical Altstadt. I love going on hikes in the unique Sächsische Schweiz.
Also, Dresden is the best place to raise a kid! There are so many playgrounds, museums, sportive or cultural offers.
Johanna: Dresden is great for walks through parks, the forest and also the historic center. There are also several people of the institute that organise free time activities such as volleyball, soccer or improv theatre.
Ornella: Dresden has it all! You can go on awesome hikes or bike rides surrounded by beautiful nature. In the lively Neustadt neighborhood, you can hang out, grab a drink or beer, and have a great time with friends. If you’re into techno music, Dresden is the place to be!
Browse through other ‘Lab meeting’ posts featuring developmental and stem cell biology labs around the world.
In our latest SciArt profile, we spoke to Frank Macabenta, a developmental biologist who freelances as a scientific illustrator. Franks share with us his lab’s work on quality control mechanisms regulating organogenesis in the fly embryo, and how art influenced his decision to pursue studies in developmental biology.
Can you tell us about your background and what you work on now?
I am an immigrant and first-generation scientist. My family emigrated from the Philippines to the island of Guam when I was very young, which is where I lived for most of my early life. I studied biology at the University of Guam, initially with aspirations of going to medical school; however, after trying out research in Dr. Mari Marutani’s vegetable horticulture lab at the UOG College of Agriculture and Life Sciences, I decided to change my trajectory and focus on pursuing a career in research. I wasn’t sure what I ultimately wanted to study, but I was lucky enough to be selected for a summer research opportunity at Rutgers University just before starting my senior year, where I worked in the lab of Dr. Sunita Kramer. I fell in love with the Drosophila model system and developmental biology in Sunita’s lab, where we used confocal microscopy to study heart tube formation in the embryo. I ended up applying for grad school at Rutgers, where I conducted my doctoral thesis work in Sunita’s lab. After obtaining my PhD, I decided to stick with Drosophila as a model system (while also seeking warmer climes!) and worked as a postdoc in Dr. Angelike Stathopoulos’ lab at the California Institute of Technology, where I studied the genetic programs that guide the collective migration of a small population of muscle precursors in the Drosophila embryo called the caudal visceral mesoderm (CVM). CVM cells undergo collective migration along the length of the embryo to form the longitudinal fibers of the larval midgut muscles. We not only identified a number of complex multi-tissue interactions that drive CVM collective behavior, but also learned a lot about the intersecting signaling pathways that control growth and cell death to ensure stereotyped assembly of these muscles. I am currently an Assistant Professor at the California State University, Monterey Bay, where I teach both introductory and advanced courses in general and developmental biology, as well as run a research lab where we continue to study quality control mechanisms regulating organogenesis in the fly embryo.
Genesee Scientific Fly Art commission, titled “Drosophila steampunkii.” Created with GIMP.
Were you always going to be a scientist?
I definitely believe I was always going to be pursuing science in some capacity — since I was a little kid, I enjoyed going out in the yard to observe and collect various insects, or making a mess in the kitchen after seeing some experiment demonstrated in a TV show (often to my mother’s chagrin!). My parents encouraged and nurtured my love for science by buying every book, even gifting me with a simple compound microscope and slide-making kit — however, in my culture, children who have an affinity for science are typically expected to pursue a degree in medicine. I rationalized the choice of studying to become an MD as a career path that would still allow me to do science, and held onto this aspiration all the way up to college. However, my first research experience at the University of Guam under the auspices of an NIH Research Initiative for Scientific Enhancement (RISE) program, combined with some conversations with my professors convinced me to fully embrace scientific research as a career goal.
And what about art – have you always enjoyed it?
Art has always been a passion of mine. Growing up as an only child with few children my age in the neighborhood, drawing was an outlet that allowed me to express my imagination. Like my love for science, my parents also indulged my love for art — I’ve dabbled in pretty much every medium while growing up. Art also influenced my decision to pursue studies in developmental biology; I was awed by the beautiful high-resolution images that one can obtain of immunostained tissues. In a way, developmental biology research combines two of my greatest passions!
A cell cycle-coupled quality control system for migrating embryonic muscle precursor cells in Drosophila illustrated as Persephone, the dual goddess of Spring and the Underworld. The image depicts how cells either undergo continued growth and myogenesis after cell division, or programmed cell death. Created with Adobe Illustrator.
What or who are your most important artistic influences?
I would say I’m heavily influenced by detailed sci-fi/fantasy art. Growing up, I admired the works of artists like James Gurney, who combined meticulous depictions of dinosaurs with fantastical scenes for ‘Dinotopia,’ evoking a world where humans and dinosaurs coexist. As a cell biologist, I also greatly admire the work of Dr. David Goodsell — his ability to bring biomolecules and the spectacular, microscopic worlds they inhabit represent a truly elegant union of science and art!
How do you make your art?
I typically use black and white media like pencil and pen on paper for sketches and such. Some time back I bought myself a drawing tablet and started dabbling in digital art. I didn’t go through any formal training, so it’s been a lot of trial and error for me. I used to use the GNU Image Manipulation Program to make pieces, but I’ve since moved on to using Adobe Illustrator or Adobe Photoshop.
A stylized illustration of a gynandromorphic fly, depicting a friend’s discovery of a mechanism for piRNA-dependent regulation of sexually dimorphic traits in Drosophila. Created with Adobe Illustrator.
Does your art influence your science at all, or are they separate worlds?
Art definitely has a profound influence on my field of research! Throughout the grad school and postdoc phases of my career, I often illustrated figures (and occasionally cover art) for manuscripts in addition to benchwork. My lab studies how embryonic muscles undergo precise and highly-stereotyped patterning, so my group spends a lot of time collecting images of immunostained cells. Scoring defects in muscle assembly takes quite a bit of observation and pattern recognition, which are skills that both artists and developmental biologists use regularly. Trying to understand the various phenotypes we observe also takes quite a bit of creative thinking — I think a lot of people underestimate how big a role imagination plays in planning and executing studies!
What are you thinking of working on next?
I’m thinking of creating more fruit fly-related work. I love the Drosophila research community, and want to inspire my students to see the beauty in studying developmental biology through model organisms like the fruit fly!
I became interested in the evolution and development of skin appendages (such as scales, spines and feathers) during my PhD with Dr. Gareth Fraser, when I was studying the patterning of scales and teeth in the shark. I wanted to continue working in this field, and luckily the LANE(Milinkovitch-Tzika lab) advertised a postdoc position at just the right time. This lab is renowned for studying skin appendage development in really diverse non-classical models such as snakes, lizards and exotic mammals, so it was the perfect destination for me. One key finding by Michel Milinkovitch & his then post-doc Nicolas Di-Poï, was that not only hair and feathers, but also reptilian scales, develop from placodes – localised thickenings of the skin that constitute the foundations of most skin appendages (2). When I arrived in the LANE in 2020, there was already an ongoing project investigating chicken scale development, so it was easy for me to get started straight away.
What was already known about ectopic feather induction in chicken embryos?
There have been a few published articles reporting a scale-to-feather conversion in the chicken embryo (3-5). However, the results of these studies are variable. First, not all of these scale-to-feather conversions result in true, regenerative feathers, second, the coverage of these ectopic feathers was not ubiquitous, and third, the post-embryonic development of these feathers had not been examined. Also, our lab had recently developed a really nice protocol for injecting precise quantities of drugs directly into the veins of developing chicken embryos (as well as other hard-shelled eggs) (6). You can check this out in the video below. This project provided a great opportunity to try out this method.
Intravenous injection protocol for treating hard-shelled amniote eggs (Cooper et al. 2023)
Can you summarise your key findings?
We investigated the role of the sonic hedgehog (Shh) pathway in mediating skin appendage fate in the chicken. This pathway is essential for loads of developmental events, and is really important in controlling the early development of placodes. We injected a precise dose of a Shh pathway activator directly into the blood stream of developing embryos (6), at the exact time that scales begin to appear on their footpads. We then collected the embryos at various stages after injection, and even allowed some to hatch so that we could examine the effect in adult chickens. Incredibly, every single chickens injected with the Shh activator had abundant ectopic feathers covering their feet. We tracked the development of these ectopic feathers in hatched chickens, and saw that they transitioned from juvenile down-type feathers into true contour feathers observed in adult birds. This confirmed that our experimentally-induced feathers are true, regenerative feathers.
When doing the research, did you have any particular result or eureka moment that has stuck with you?
I distinctly remember looking at the first treated sample under the microscope – it was collected after 4 days, meaning that the ectopic feather buds were still relatively undeveloped. At first glance it looked like an incredibly hairy chicken foot. I showed the sample to my boss, and he suggested that we should see what happened if we allowed the embryos to develop until hatching. A few weeks later we had our first feather-footed hatchling chickens!
And what about the flipside: any moments of frustration or despair?
Whilst attempting to harvest samples for RNAseq, the treatment suddenly began to kill all of the embryos. As there was a short power outage in our lab during the incubation of the eggs, I initially assumed that the embryos were slightly less developed than before. I then repeated the experiment with fresh eggs, and exactly the same thing happened. Finally, I contacted the farmer who provides the eggs, and he told us that they had just replaced their laying hens, meaning that the eggs were now coming from much younger chickens, which lay much smaller eggs. After adjusting the treatment to account for this change, the experiment worked perfectly.
What is next for you after this paper?
I’m working on some more really exciting skin appendage-related projects in the Milinkovitch-Tzika lab. We have an additional manuscript on chicken scale development in the pipeline, and Michel has had me heavily involved me in another project on crocodile scale patterning – they’re both really cool stories, and hopefully we will be able to share them with you soon!
References
1. R. L. Cooper, M. C. Milinkovitch, Transient agonism of the sonic hedgehog pathway triggers a permanent transition of skin appendage fate in the chicken embryo. Science Advances9, eadg9619 (2023).
2. N. Di-Poï, M. C. Milinkovitch, The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes. Science Advances2, e1600708 (2016).
3. D. Dhouailly, M. H. Hardy, P. Sengel, Formation of feathers on chick foot scales: A stage-dependent morphogenetic response to retinoic acid. Journal of embryology and experimental morphology58, 63-78 (1980).
4. R. B. Widelitz, T. X. Jiang, J. Lu, C. M. Chuong, Beta-catenin in epithelial morphogenesis: conversion of part of avian foot scales into feather buds with a mutated beta-catenin. Dev Biol219, 98-114 (2000).
5. P. Wu et al., Multiple Regulatory Modules Are Required for Scale-to-Feather Conversion. Mol Biol Evol35, 417-430 (2018).
6. R. L. Cooper, G. Santos-Duran, M. C. Milinkovitch, Protocol for the rapid intravenous in ovo injection of developing amniote embryos. STAR Protocols4, 102324 (2023).
How stem cells decide to choose between two conflicting fates, division vs. differentiation, is an unsolved mystery of stem cell biology. The overarching goal of Shariati lab is to determine the mechanisms that link cell division to cellular differentiation in pluripotent cells. We will combine emerging genome-editing technologies with single cell imaging to determine regulatory principles of cell fate decisions in pluripotent cells.
Applicants with demonstrated experience in any of the following areas are highly encouraged to apply: Stem Cell Biology, Transcription, Quantitative Single Cell imaging, CRISPR screening and Mouse Genetics. The potential start date is Fall 2023.
As your postdoc advisor, I will support you to reach the career goals that you set for yourself. In addition, UCSC has exceptional career development programs for postdoctoral fellows. Santa Cruz is a great town for postdocs as you can easily refresh your mind by strolling in beautiful redwood forests on campus or going to one of the many nearby beaches. Please email me (alish {a} ucsc.edu) a cover letter stating your scientific background and interest, your CV and names/addresses of your advisors.
Applicants from underrepresented groups in sciences are highly encouraged to apply. Informal inquires also are welcomed!
Heart failure occurs when the heart is weakened or damaged, or when there is a problem with the heart’s valves or rhythm. Strikingly, it is the leading cause of hospitalisation and deaths in men and women worldwide. Nevertheless, significant gaps remain in our understanding of heart failure, and treatment, at best, results in disease remission. Our goal in shaping this Special Issue of Disease Models & Mechanisms (DMM) was to compile original Research, Resource and Review-type articles that investigate the genetic and biological mechanisms of heart failure and identify potential therapeutic strategies, as summarised in an Editorial from Guest Editors Jeroen, Milena Bellin and Ravi Karra.
Guest Editors Jeroen Bakkers, Milena Bellin and Ravi Karra
A significant risk factor for heart failure is congenital heart defects, which are structural abnormalities affecting 8 out of every 1000 new-borns. The causes of congenital heart defects are diverse, which encourages the exploration of these disorders in the context of cardiac development. A Review from Christian Mosimann’s group summarises how defects in lateral plate mesoderm development drive congenital defects of multiple organs, including the heart, and a Research article from Didier Stainier and colleagues uses zebrafish to study the role of the epicardium, the outermost layer of the heart, in coordinating growth of the myocardium. Sally Dunwoodie and colleagues also published a study on a metabolic disease that results in congenital heart malformation.
Beyond disordered heart development, arrhythmias, which occur due to disruptions in the heart’s electrical system, represent another risk factor for heart failure. A Review by Vincent Christoffels and colleagues, published in this issue, explores the genetic causes of heart arrhythmias. Another Review from Eva Van Rooij’s group discusses the use of precise genome editing to generate models of and to potentially treat cardiomyopathies, which involve the remodelling of heart muscle and can also lead to heart failure if left untreated.
This special issue also provides an insight into the current understanding of acquired heart disease, with studies ranging from the investigation of strategies to mitigate cardiac remodelling upon injury to how the gut microbiome metabolite trimethylamine-N-oxide affects heart function.
Finally, the Special Issue includes ‘A Model for Life’ interview between leading experts Jeroen Bakkers and Didier Stainier, who discuss the advantages and disadvantages of zebrafish models of heart disease. Model organisms, both large and small, have been instrumental in advancing this field, with articles in this Special Issue using or discussing the use of mice, rats and pigs as valuable models of heart failure with strong translational potential. In addition, in vitro models, such as organoids, will provide new research opportunities to study cardiac development and related diseases, as summarised in the beautiful At a Glance poster article by Lika Drakhlis and Robert Zweigerdt and in ‘A Model for Life’ interview with Professor Christine Mummery. The Research, Resource and Review-type articles in this Special Issue cover a wealth of seemingly diverse topics. However, preventing, understanding and treating heart failure are the common threads that bind these articles. Follow the link below to read all the articles in this Special Issue for free.
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