Update 10/1/23: more on this meeting in The Lonely Pipette “Why do we go to conferences?“

What an exciting time to be studying embryonic development! Emerging experimental systems, methods and analyses allow addressing a whole new set of fascinating questions, as well as revisit older ones. In particular, the field of patterning and morphogenesis, which investigates how embryos establish their body plan with the correct cell types and shape, currently experiences rapid technological and conceptual transformations. For example, microfluidics and microfabrication now permit manipulating the culture conditions of developing embryos with extended flexibility; organoid systems allow the reconstitution of tissues and structures entirely from stem cells; microscopy methods such as light sheet microscopy, live sensor of signalling pathways, optogenetic tools allow dissecting developmental mechanisms over unprecedented temporal and spatial scales. Together, these new possibilities will be key to structure the field of patterning and morphogenesis over the next decades. This research will be carried out, in part, by a new generation of emerging leaders. From July 25th to 29th of 2022, scientists who recently established their labs in Europe gathered in Les Treilles to discuss the emerging quantitative approaches to study embryonic development. From nematodes, flies, sea urchin, frogs, zebrafish, cow and mouse to human, a broad variety of developmental processes were covered from fertilization to organogenesis.

Observing embryonic development is key to understand it.

Technological developments in light sheet microscopy have allowed imaging of large-scale morphogenetic events while maintaining cellular resolution. Kate McDole, who locked herself in a room during the pandemic to build a new light sheet microscope, presented never-seen-before cell movements during mouse gastrulation, shedding light on the origin of cells constituting the different germ layers. Rita Mateus also used light sheet microscopy to image the patterns involved in the formation of the zebrafish pectoral fins and better characterise how those patterns scale during growth and regeneration. As the fins emerge, other organs, like the heart, also form complex structures such as the muscular trabecular ridges that enable proper heart contraction. Using quantitative live imaging and clonal analysis, Rashmi Priya explained how complex tissue architecture is built during trabecular morphogenesis. Zebrafish was also at the heart of Diana Pinheiro’s work, as she reported on a mechanism explaining the coordination of mesoderm progenitors migration and specification by Nodal signalling during gastrulation. When missing, Nodal signaling causes characteristic phenotypes that expert zebrafish embryologists can easily recognize. Patrick Müller leveraged deep learning analyses to develop algorithms that outperform embryologists at identifying the phenotypes of zebrafish gastrulation mutants.

Together, these studies show how imaging large-scale shape changes and quantitatively tracking them can help understand the global patterning and morphogenesis of embryos.

Down to the sub-cellular scale, high resolution microscopy reveals the mechanisms employed by cells to shape embryos. In particular, Anne-Cécile Reymann looked into the influence and distribution of maternally deposited regulators of the actin cytoskeleton during the early cleavages of c elegans embryos. In contrast, Tommaso Cavazza reported on how microtubules help coordinate chromosome segregation in cow zygotes before the nuclear envelope of the parental pronuclei breaks down. Later during mammalian development, Jean-Léon Maître described how protrusions help cells control the formation and positioning of a fluid-filled lumen that helps setting the first axis of symmetry of the embryo. A different set of protrusions was introduced by Jakub Sedzinski to explain how cells can insert themselves within epithelia and increase the complexity of tissues. Finally, peering into fly embryos, Timothy Saunders quantified the scaling of Bcd gradients by combining fluorescence correlation spectroscopy and mutants affecting egg size.

Altogether, bridging the sub-cellular scale to embryonic changes is key to understand the molecular and physical regulation of embryonic development.

Probing and challenging embryos in novel ways

Exploring how cells change their chemical composition and physical properties during development will help understand their behaviour. Mariaceleste Aragona quantitatively analysed the effect of tissue stretching in vivo using clonal analysis and single cell sequencing to understand how cells change composition and fate after a long-term physical perturbation. To understand how cells sense mechanical perturbations, Verena Ruprecht investigated the short-term response of cells to compression by combining high resolution microscopy, microfabrication and optical tweezers. Tweezers were also on the menu for Nicolas Minc who developed magnetic tweezers strong and precise enough to move the entire mitotic spindle within cells to induce division asymmetries and explore the mechanics of the cytoplasm.

Understanding how embryos develop requires the need to finely perturb this process in controlled ways. Romain Levayer leveraged the powerful genetics of Drosophila and optogenetics to induce the death of a precise number of cells and determine the range of robustness of epithelia to cell delamination. Another way to control in space and time the molecular regulation of embryonic development is microfluidics: using precise oscillations of chemical compound, Ina Sonnen could explore the coupling of biological clocks during somitogenesis. Finally, Elias Barriga measured endogenous electric fields and applied electric fields of similar magnitude to steer the migration of neural crest cells in Xenopus embryos.

Together, discussing the current research and future projects of young European scientists revealed the promises and challenges of applying quantitative methods to developmental biology. On the one hand, quantitative methods allow dissecting developmental mechanisms with unprecedented precision. On the other hand, the integration of multiple spatial and temporal scales, and different source of biological information (such as chemical, mechanical and electrical signals) remain extremely challenging. Moreover, tackling these problems when most biologists lack the appropriate training in mathematics and coding can be challenging. A consensus appeared regarding the need to include more biology-oriented maths in university programmes, as this will be key to anchor biology to the realm of modern science. Importantly, Renaud Pourpre, who carried out several initiatives to bring microscopy data to the public, reminded us how microscopy images constitute a straightforward avenue to communicate around science to a lay audience (see CellWorlds documentary). By the same token, there is no doubt that the beauty of developing embryos will continue motivating biologists and other scientists to expand their toolbox to decipher the mechanisms of development.

(6 votes)

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Interested in the cell or molecular mechanisms underlying disease? Do you have an outstanding record and an innovative research plan?

The Dunn School of Pathology at the University of Oxford is looking for outstanding early career researchers seeking a stimulating and supportive environment in which to establish their research group as externally-funded fellows. We are specifically looking for researchers seeking mentoring and sponsorship to apply for career development fellowships (e.g. Wellcome Trust Career Development Award, MRC Career Development Award, CRUK Career Development Fellowship, UKRI Future Leaders, etc). Researchers who succeed in securing a fellowship will then be invited to establish their independent group in the department, benefiting from a generous support package, comprehensive mentorship, career development training and opportunities to recruit Oxford undergraduate and postgraduate students.

Successful candidates will have an outstanding track record in any area of biomedical research, with a particular focus on the fundamental cell and molecular biology underlying disease. The Department celebrates diversity and we welcome applicants from diverse backgrounds that are currently underrepresented at the University of Oxford.

More information and contact for informal queries can be found on our website: https://www.path.ox.ac.uk/content/cdf The deadline for applications is the 12^th of October 2022.

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Are you just starting out in your career as a developmental biologist (or feeling nostalgic for those times)? The vast amount of literature can feel a bit daunting when you are tackling a new topic. To help you navigate the field, and to focus on some of the lesser known classics, we asked prominent researchers to recommend their hidden gems from history. Their selection includes Rosa Beddington’s chimeras, Morgan’s planarian experiments and principles of morphogenesis from Gustafson and Wolpert. Let us know if you come across any forgotten classics that we should include in our series.

(3 votes)

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“Imagine a society where female reproductive rights are a matter of state concern. Where working class females are actively suppressed from having their own children, and only the nobility are allowed to reproduce. I am, of course, talking about honey bees.”

Dr Sally Le Page

In the latest episode of the Genetics Unzipped podcast, Dr Sally Le Page looks at the genetics of societies, exploring how genes underpin the rigid social structures and roles in bees, and how they can rise up the ranks to become queen bee.

Genetics Unzipped is the podcast from The Genetics Society. Full transcript, links and references available online at GeneticsUnzipped.com.

Subscribe from Apple podcasts, Spotify, or wherever you get your podcasts.

Head over to GeneticsUnzipped.com to catch up on our extensive back catalogue.

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

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Read on for our news roundup of the past few weeks, with an emphasis on what has caught our eyes on twitter. This post is focussed on career advice, conferences and related conversations.

Advice for students (and their supervisors!)

Looking for faculty positions

Development’s ‘Transitions in development’ interviews are full of useful nuggets of information for those looking for faculty positions, as well as helpful tips for starting your lab.

Moving to industry

Earlier this year, we heard from Dhruv Raina about his move to industry following his PhD in  Dr Christian Schröter’s lab at the Max Planck Institute of Molecular Physiology (MPI).

For the latest job listings at all levels, including an opportunity for a new Features and Reviews Editor at Journal of Cell Science, check out our active jobs board.

Conferences

The return to in-person conferences has been wonderful, but what have we learnt due to the restrictions imposed during lockdowns, and how can we improve future conferencing?

We are delighted to be live–streaming our session on recent recent progress and ethical challenges in studying early human development from our upcoming meeting, From Stem cells to Human Development on Monday 12 September 16:00 BST. More details will follow on the Node shortly.

In vitro models of development have been a talking point on Twitter in the last few weeks. The thread from Dr Martinez Arias sums up some of the key points.

Our Special Issue: Modelling Development in vitro is open with some fantastic articles already available, and we will be adding more over the coming months.

preLights in Development

Too crowded for comfort: cells in confinement stop proliferating to maintain proper tissue architecture, but how? Devany and colleagues present a quantitative framework to address this question.

Changes in gene expression and physical form are intricately linked during development, but how do we begin to measure both on a continuous timescale? Mitchell et al provide a path forward with their Morphodynamic Atlas

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We are arranging a 2-day conference together with the Swedish Society for Developmental Biology (SWEDBO), Finnish Society for Developmental Biologists, and Danish & Norwegian Developmental Biologists the 3rd Nordic Meeting on Development, Stem Cells and Regeneration in Copenhagen in October 5-7th, 2022

The line up of invited speakers is outstanding and brings together experts in developmental and stem cell biology and regeneration! Attending the meeting is a great opportunity to meet with developmental biologists, from the Nordic countries and beyond. All speakers will be there ‘in person’ allowing for lots of networking.

There are many opportunities for short talks, poster prizes, and student and postdoc activities are planned in addition.
The registration is now open and it includes membership in one of the Nordic Developmental Biology associations!
Follow the link to register: https://nordicdevelopmentalbiology.com

Travel grant applications are still open: https://nordicdevelopmentalbiology.com/travel-grants/

I really hope that some of you will come to Copenhagen and join us.

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Dr. Denise Allen and Dr. Tomasz Nowakowski at the University of California, San Francisco recently published an article in Science where they revealed a dual origin for astrocytes in the human cortex. Using a combination of fate mapping and single cell analysis, they revealed that the two stem cell niches in the developing cortex give rise to spatially, morphologically, and molecularly distinct populations of astrocytes. The Node asked them to give us a behind the scenes look at how the story came together:

1. How did you get started on this project?

TJN: For a very long time, we have been interested in the question of why the brains of primates and humans are so much larger and complex than the brains of mice, which we study frequently in the laboratory. Differences in brain size can be found very early on during development, and therefore it was plausible to hypothesize that differences in the way radial glia, which act as neural stem cells, develop could contribute to these differences. In our prior work, we found that animals with large brains, such as primates or humans, contain a greater diversity of radial glia subtypes compared to mice. In particular, we found that based on gene expression profiles, radial glia could be divided into truncated radial glia and outer radial glia, which are located in two anatomically distinct niches of the developing cortex.

DA: During my undergraduate neuroscience classes I was always struck by the deep knowledge we have about the development of neurons in the cerebral cortex, but astrocytes and other glia seemed to be so often overlooked. During my rotation in the Nowakowski lab, I became fascinated with Tom’s preliminary data that suggested distinct subtypes of radial glia could give rise to distinct astrocyte populations. I was really excited by the fact that large brain mammals, including primates and humans, seem to have a different repertoire of radial glia compared to rodents, as well as much more complex astrocytes.  So the possibility to study the unique features of human development with a focus on astrocytes was a dream come true.

2. What was already known about the developmental trajectories of radial glia in the developing brain prior to your work?

A lot of work has been done probing the differentiation of outer radial glia (also known as basal radial glia). Numerous papers have shown that they give rise to neurons, oligodendrocytes and supposedly the majority of astrocytes, but the role of truncated radial glia has not been studied in great detail. Previous studies have suggested that because few mitotic cells can be found in the ventricular zone stem cell niche during midgestation in primates and humans, that the truncated radial glia that reside in this zone are unlikely to serve as a major source of new cells. We decided to challenge this assumption by labeling progenitors in the ventricular zone and determining the fates of the resulting cells. To our surprise, we found that  neurons, oligodendrocytes, and astrocytes continue to be produced by ventricular zone progenitors. 

3. Can you summarize your findings? What was the key experiment?

The key experiment involved labeling progenitor cells that occupy anatomically distinct niches that truncated and outer radial glia cells, and tracing the fates of cells that they produce. We found that while  both populations broadly produce similar cell types (neurons, astrocytes and oligodendrocytes), they produce very distinct subtypes of astrocytes. In a series of very striking results, we found that truncated radial glia give rise to astrocytes that migrate to the cortical plate, while outer radial glia give rise to astrocytes that do not migrate, and instead differentiate locally in the outer subventricular zone.  

We often speak about the diversity of neurons, but classical studies have also shown that astrocytes can be remarkably diverse, even in early development. I wanted to further explore the diversity of the astrocyte subtypes we identified, but it is challenging to connect these classical descriptions of astrocyte subtypes to modern-day descriptions such as those derived from  single cell sequencing. To solve this problem, I took advantage of a method called Patch-seq which gave us the ability to aspirate the contents of a cell that was previously defined based on its morphology and position, and then performing sequencing of that cellular contents to determine a molecular identity. This analysis was key for bridging our cellular definitions based on morphology and developmental cell lineage, and linking them to molecular markers. This allowed me to bring the story in full circle. 

4. When doing the research, did you have any particular result or eureka moment that has stuck with you?

The very first experiment I performed that involved labeling these two different stem cell niches resulted in a distribution of cell types that could not have been more different.  Many comparisons in developmental biology rest upon small differences between conditions.   To see such a stark difference in the distribution of cells–especially of glia–was an exciting moment that defined the course of the project very early on in my PhD.

Another surprising finding was when we started closely comparing classical drawings by Ramon y Cajal and Retzius and to images of our astrocyte subtypes. Remarkably, we found that our “dense bulbous” astrocytes were clearly depicted in those early records, but these cells have rarely been mentioned in modern literature. This realization gave us a lot of confidence that the cells we were observing were a real phenomenon and not an experimental artifact. These cells had just been lying in wait, waiting for someone to put the spotlight on them.

5. And what about the flipside? Any frustrations or despair?

The Universe really conspired against us when we were trying to finish experiments for the revision of the paper. I set up the last three revision experiments in late December, when we suddenly found out that it was time to move our lab to a new building at UCSF. We came up with an elaborate system to keep the cultures going while we moved and they seemed to have survived, until someone suddenly noticed that the incubator had failed and the alarm hadn’t gone off. What followed was two months of issue after issue trying to repeat these last two experiments, but we finally got there in the end!

6. Where will this story take the lab?

This work has inspired several new projects in the lab. We are excited to examine if similar findings can be replicated in other models of brain development such as cerebral organoids, what these unique subpopulations look like in the adult brain, and what role they might play in disease states. I’m also hoping this work will also attract more trainees interested in glial development to the lab! 

7. What is next for you/the lab after this paper? Let us know if you are continuing this research, or starting/looking for a new position.

Denise has graduated and is currently interviewing for computational biologist roles in biotech. She is looking forward to delving into the “big data” side of biology, and working towards making a significant impact on patients’ lives.

(1 votes)

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Development’s biennial meeting, From Stem Cells to Human Development, will be taking place in mid-September (11-14) at beautiful Wotton House in Surrey, UK. After a very successful virtual meeting in 2020, we’re excited to be meeting in person again, but we wanted to explore ways of making part of the meeting accessible to the broader community. We’re therefore delighted to announce that we’ll be livestreaming one session of this meeting, and the recording is available below.

Session details (all times GMT+1):
16:00 Sarah Teichmann (Wellcome Sanger Institute, UK): Human development: one cell at a time
16:30 Sergiu Pasca (Stanford University, USA): From stem cells to assembloids: constructing and deconstructing human nervous system development and disease
17:00 Panel discussion: Technical, ethical and legal challenges of studying early human development
Chair: Patrick Tam (University of Sydney, Australia)
Panellists: Amander Clark (University of California Los Angeles), Robin Lovell-Badge (The Francis Crick Institute, UK), Sergiu Pasca, Sarah Teichmann, Magdalena Zernicka-Goetz (University of Cambridge, UK and CalTech, USA)
18:00 Close

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The method was straightforward: take a bunch of writers, novelists, a playwright, science communicators and scientists from all over the world, from fields as diverse as astrophysics and climate science to materials engineering, neurobiology, and evolution, confine them to a 16^th century manor, and get them talking. The result: The Company of Biologists’ whacky and wonderful Creative Science Writing Workshop. 

Good scientific writing has the power to help communities make more informed decisions, and a creative route could make it more accessible and exciting for all. But here, without the certainties of a regular science meeting where everyone shares a common interest in a method, organism or question, and data and information that forms the focus of most scientific discussions, what would happen was anyone’s guess. 

Any disquiet quickly evaporated in the opening session where everyone introduced themselves through stories, childhood memories, and mementos:  a bottled book, a handmade urn, the steady pulse of a ticking metronome, the clinking beads of a treasured necklace, a traditional Indian kolam drawn in flour before our eyes. It was immediately clear that despite our diverse backgrounds and experiences, everyone shared a passion for storytelling and science in all its forms. The Workshop began with a bang! 

The programme included a variety of topics and activities. We read S.J. Gould, Primo Levi and the brilliant Karen Joy Fowler, looking for the ingredients of great writing and pondering the authors’ process and intent. We critiqued the work of other delegates, providing structured feedback – a rather nerve-racking exercise when one considers the differences between academic and creative writing.  In conventional science writing, the authors present new facts and relationships that help us better understand our world, without ever revealing themselves. In creative writing the opposite holds true; every piece exposes the writer, their style, their quirks of character, beliefs, and passions. This Workshop managed the juxtaposition remarkably well. 

There were also sessions on structuring writing, getting published, and the role of agents. Most importantly, there was time to write, review, and revise. Inside oak-panelled rooms, within the verdant grounds, and in the sunny conservatory, relationships grew, word counts climbed, and inspiration abounded.

Over a period of three and a half days, the Workshop exposed delegates to the world of writing and publishing. Aspiring writers learned from one another as well as from the established writers – who were incredible mentors. It was a journey that traversed science and writing, lab and the field, life and the page, lyrical prose and cold hard facts. In doing so, a new community was formed. 

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Applications will remain open until the position is filled.

The Gambetta lab is recruiting a Postdoctoral researcher to study how genome architecture impacts gene regulation in development.

Project

The advertised project addresses the fundamental question of how regulatory elements are guided to their target genes. You will study a paradigm we uncovered in which genes are controlled by regulatory elements located at flexible and surprising large genomic distances. This model is powerful and unique.

You will use genetics (Drosophila genome-engineering, genetic screens, comparative evolution), genomics (transcriptomics, chromatin accessibility, chromosome conformation capture, genome-wide screens, single-cell genomics), imaging (fixed and live), and biochemistry (proteomics).

This work is expected to continue to reveal new evolutionary perspectives into the relevance of 3D genome folding for correctly wiring genes to their regulatory elements. For more information on our research check our lab website: http://www.gambettalab.org

Job information

Expected start date in position : as soon as possible or to be agreed

Contract length : 1 year, renewable 2 x 2 years, maximum 5 years

Your responsibilities

You will use multidisciplinary approaches such as genomics, genetics, imaging, and/or biochemistry in the fruit fly Drosophila melanogaster. You will present your results during seminars with gene regulation research labs in Lausanne. You will collaborate with other labs in Lausanne and abroad. Full funding for the position is available, but application to fellowships is also expected.

Your qualifications

You are a dynamic and rigorous scientist with a PhD degree in Biology or a related discipline. You have experience in genomics (next-generation sequencing library preparation), molecular biology, genetics, biochemistry or imaging. You are a critical thinker, a team player eager to participate in scientific discussions but able to work independently. You have a strong interest in developing your skills in multidisciplinary experimental strategies to understand basic mechanisms in gene regulation.

Your benefits

The Gambetta lab is hosted at the Center for Integrative Genomics (CIG) at the University of Lausanne (UNIL), a vibrant, well-funded institute with a focus on functional genomics and equipped with modern core facilities (see www.unil.ch/cig).

It is embedded in the broader Lausanne research environment that includes two universities (UNIL, EPFL), the Swiss Institute of Bioinformatics, Ludwig Center for Cancer Research, university hospital, and a cluster of biotech companies flourishing in the larger lake Geneva area.

The Gambetta lab tightly networks with other gene regulation research laboratories at UNIL and EPFL, and collaborates with the on-site Bioinformatics Competence Center. There are regular possibilities to present and participate in local or international conferences and workshops. Hard and soft skill, and career development courses are offered on campus.

We offer a nice working place in a multicultural, diversified and dynamic academic environment.

Your application

Please email lab head Prof. Maria Cristina Gambetta (mariacristina.gambetta@unil.ch). Provide your CV, a brief description of your research experience, and why you think your research interests complement ours.

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