La biologie du développement au XXIème siècle/ Developmental biology in the 21st century

Seminar organized by Alain Chédotal (Institut de la Vision, FR) and Olivier Pourquié (Harvard University, USA) from 3 to 8 July, 2023.

Participants

James BRISCOE (Francis Crick Institute, London, UK), Alain CHEDOTAL (Institut de la Vision, Paris, France), Claude DESPLAN  (New York University, USA), Margarete DIAZ CUADROS (Harvard University, Massachusets, USA), Denis DUBOULE (EPFL, CH & Collège de France, Paris, France), Joaquina VIVES DELAS (Francis Crick Institute, London, UK), Paolo GIACOBINI (Lille Neuroscience and Cognition, France), Megumi INOUE (Institut de la Vision, Paris, France), Mounia LAGHA (Institut de Génétique Moléculaire de Montpellier, France), Lakshminarayanan MAHADEVAN  (Harvard University, Massachusets, USA), Yuchuan MIAO (Harvard University, Massachusetts, USA), Olivier POURQUIE (Harvard University, Massachusets, USA), Alex SCHIER (Biozentrum University of Basel, CH), Elena SEIRADAKE (University of Oxford, UK), Andrew SILBERFELD (Harvard University, Massachusets, USA), Shankar SRINIVAS (University of Oxford, UK), Magali SUZANNE (CBI Toulouse, FR), Maria-Antonietta TOSCHES  (Columbia University, USA), Barbara TREUTLEIN (ETH Zurich, CH)

Résumé

Le séminaire “Biologie du développement au 21e siècle”, qui s’est tenu du 3 au 8 juillet 2023, a rassemblé des biologistes du développement travaillant sur un large éventail de sujets et d’organismes, facilitant ainsi l’établissement de nouveaux liens et les discussions sur l’avenir de la biologie du développement. Les nouvelles technologies et méthodes nous permettent de poser des questions et d’y répondre aux niveaux moléculaire, cellulaire, tissulaire, organique et enfin au niveau de l’organe entier, et d’intégrer les observations à toutes les échelles. L’analyse des transcriptomes au niveau de la cellule unique a redéfini les types de cellules, révélant de nouveaux états et types cellulaires au cours du développement. Les systèmes avancés d’organoïdes et de culture permettent d’obtenir des informations sans précédent sur les mécanismes des processus de développement. Les technologies d’imagerie à haute résolution et les applications de l’intelligence artificielle dans les analyses d’images permettent de nouvelles observations couvrant de multiples dimensions. Quelle période passionnante pour être biologiste du développement !

Abstract

Photo d’un embryon de serpent imagé en 3D (les nerfs sont en cyan et certains neurones sont visible en magenta)/ 3D picture of a snake embryo (nerves are in cyan and some neurones in magenta)

Developmental Biology in the 21st Century, July 3-8, 2023, brought together developmental biologists working on a diverse range of topics and organisms, facilitating new connections and discussions on the future of developmental biology. New technologies and methods allow us to ask and answer questions from the molecular, cellular, tissue, organ, and finally whole organ levels and integrate observations across scales. Single cell analysis of transcriptomes have redefined cell types, revealing novel cell states and types across development. Advanced organoid and culture systems allow unprecedented insight in mechanisms of developmental processes. High resolution imaging technologies and applications of artificial intelligence in image analyses allow for new observations spanning multiple dimensions. What an exciting time to be a developmental biologist!

Report

On the first day, James Briscoe (Crick Institute, UK) started the seminar with a talk on the “What / when / how of developmental biology,” showing work on the patterning of gene expressions that organizes the formation of the neural tube (spinal cord) in the embryonic mouse. He presented a new method to study gene expression dynamics through metabolic labeling and single cell analysis and navigating the spaces of tissue, gene expression, and cell identity decision making. Magali Suzanne (CBI Toulouse, FR) presented work on the role of apoptosis in morphogenesis. Through live imaging, genetics, and biophysical modeling in two systems – leg folding in drosophila, and chicken neural tube formation – her group is asking how the bodies of organisms acquire their shape in development. Megumi Inoue (Institut de la Vision, FR) showed work on branching morphogenesis in early human lung development through 5-12 post-conceptional weeks using whole mount immunostaining, tissue clearing, and light sheet imaging. She utilized readily available commercial and open source tools to develop an image processing pipeline to produce 3D reconstructions and extract quantitative information from the branching airways. Alex Schier (Biozentrum University of Basel, CH) noted that now is the most exciting time to study developmental biology. His work on “how genes build specialized cells” used known protein-protein interactions and similarity in expression patterns to create networks of genes – termed “modules” – to describe macro-level activities that a cell performs during differentiation.

            The next day started with a presentation from Barbara Treutlein (ETH, Zurich) whose lab uses human neural organoids from pluripotent stem cells to study development of the human brain. These organoids beautifully recapitulate apical-basal patterning of the developing human cortex and can be used to better understand the epigenetic regulation of cortical layering, expansion and migration. Mounia Lagha (Montpellier, FR) spoke about her lab’s work studying precise temporal and spatial control of gene expression during development. Her lab has implemented new tools allowing for the direct imaging of both transcription and translation, allowing them to identify differential translation rates in developmental genes based on the intracellular localization of the mRNA to either the apical or basal aspect of the cell. Alain Chedotal (Vision Institute, FR) showed applications of 3-dimensional protein-labeling, followed by optical clearing and 3D imaging toward studying development of the human embryo. Such studies contrast against classical work which is largely done using 2D sections that were reconstructed. In particular, this 3D approach produces extremely high resolution images for observing development of the human head including lacrimal glands, nerves and muscles, and is further being used toward creating an atlas of the developing human head at cellular resolution. Lakshminarayanan Mahadevan (Harvard University, USA) presented examples of how principles in physics influence the patterning of shapes from plants to gastrulation. In his talk, he highlighted the interaction between gravity and differential growth at key points in a plant’s branching to produce postural correction in the growing branches. He also presented how non-local feedback is used to stabilize structures such as leaves to maintain their rigidity. Elena Seiradake (Oxford, UK) studies the molecular mechanisms of neuronal migration in mouse cortical development. Her group studies how cell guidance receptors interact with different extracellular guidance cues. Their recent work in structural biology revealed a new role for Unc5, a receptor for netrins which are involved in axon guidance. They show Unc5 interacts with GPC3, a receptor for Wnt and hedgehog signaling. Moreover, by using cell stripe assays, her lab further identified which molecular cues served as attractants or repellants of axons during migration. Andrew Silberfeld (Harvard University, USA) discussed his work studying the evolutionary and developmental origins of structural asymmetry in the mouse brain. He is applying 3D image registration toward publicly available structural imaging datasets of mouse brains to look for consistent patterns of left-right asymmetry in mice. Most regions were found to be asymmetric in each mouse dataset but the overall pattern of asymmetry varied widely across each dataset. Paolo Giacobini (Lille, FR) presented a spatially resolved single-cell genomic atlas of the fetal human nasal system. His lab accomplished this by performing single-nucleus RNA-sequencing of the developing human olfactory system over 7-12 post-conceptional weeks, and spatially located top genes using MERSCOPE. The atlas is the first of its kind describing the development of the human olfactory system, highlighting critical timepoints in development and potential biomarkers for vomeronasal receptors.

On the third day, Shankar Srinivas (University of Oxford, UK) presented his lab’s work on the morphogenesis of heart development in the mouse. During mammalian heart development, the coordinated movement of epithelial cells shape the organ but it is unclear how cell movements, rearrangements, divisions, and shape changes become integrated? His lab used lightsheet microscopy and produced a multi-embryo dataset retaining lineage and spatial information, revealing insights into the mechanisms of cell migration. Margarete Diaz Cuadros (Harvard University, USA) and her lab is studying the metabolic regulation of developmental rate in mouse and human cells. A human develops 2-3 times slower than a mouse, and developmental rate and its successful manipulation can have important implications for cell differentiation, tumor growth, and aging. She presented in-vitro models of mouse and human segmentation clocks for functional testing to determine drivers of developmental rate and revealed that the metabolic rates underlie developmental rates. Denis Duboule (EPFL, CH) presented his groups’ work on studying the mechanisms behind developmental gene regulation. Hox genes control anterior-posterior positions of expression domains and timing of activation correlates with sequence of genes. His group revealed that CTCF sites are temporal checkpoints that control the precision and pace of Hox gene expressions.

Olivier Pourquié (Harvard University, USA) began the 4th day of presentations. He discussed his groups’ work investigating the roles of metabolism in establishing the signaling gradients governing body axis elongation in the development of the musculoskeletal system. He also showed translational applications as a frontier of developmental biology, namely iPSC cell-derived skeletal muscles for muscle regeneration, and iPS cell-derived brown adipocytes to treat metabolic syndromes, hinting at an exciting future for the field. Claude Desplan (New York University, USA) presented work on the mechanisms behind neural diversity in the brain in the drosophila visual system. His group conducted developmental profiling of the optic lobes, revealing the temporal windows and new transcription factors involved in sequential specification in neuroblasts. Joaquina Delas Vives (Crick Institute, UK) studies the role of noncoding genomes in cell fate decisions. She presented her work on how cis regulatory elements affect developmental cell fate choices that lead to neuronal cell diversity in time and space. Yuchuan Miao (Harvard University, USA) presented his work building in-vitro 3D models of human somitogenesis with iPS cells. He introduced two novel culture systems termed Somitoids and Segmentoids that complement each other in the investigation of somitogenesis in differentiation, space, and time and illuminates mechanisms of somite anteroposterior patterning at unprecedented resolution. Maria Antonietta Tosches (Columbia University, USA) presented work looking at the evolutionary origins of cortical cell types, starting with a survey of the diversity of cell types across species comparing the mammalian neocortex with amphibian and reptilian. Her work has shown that the diversity of cell types are related more with input and output rather than spatial relationships. She also discussed the evolution of cortical development specifically looking at neuronal specification in the pallium in space and time.

 

Authors: Megumi Inoue, Yuchuan Miao and Andrew Silberfeld

 



Citer ce billet
ldiebold (2023, 28 août). La biologie du développement au XXIème siècle/ Developmental biology in the 21st century. Les carnets de la Fondation des Treilles. Consulté le 4 mars 2024, à l’adresse https://doi.org/10.58079/qv8h

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