The Francis Crick Institute
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Basal delamination during mouse gastrulation primes pluripotent cells for differentiation.

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journal contribution
posted on 2024-05-23, 09:21 authored by Nanami Sato, Viviane S Rosa, Aly Makhlouf, Helene Kretzmer, Abhishek Sampath Kumar, Stefanie Grosswendt, Alexandra L Mattei, Olivia Courbot, Steffen Wolf, Jerome Boulanger, Frederic Langevin, Michal Wiacek, Daniel Karpinski, Alberto Elosegui-Artola, Alexander Meissner, Magdalena Zernicka-Goetz, Marta N Shahbazi
The blueprint of the mammalian body plan is laid out during gastrulation, when a trilaminar embryo is formed. This process entails a burst of proliferation, the ingression of embryonic epiblast cells at the primitive streak, and their priming toward primitive streak fates. How these different events are coordinated remains unknown. Here, we developed and characterized a 3D culture of self-renewing mouse embryonic cells that captures the main transcriptional and architectural features of the early gastrulating mouse epiblast. Using this system in combination with microfabrication and in vivo experiments, we found that proliferation-induced crowding triggers delamination of cells that express high levels of the apical polarity protein aPKC. Upon delamination, cells become more sensitive to Wnt signaling and upregulate the expression of primitive streak markers such as Brachyury. This mechanistic coupling between ingression and differentiation ensures that the right cell types become specified at the right place during embryonic development.


Crick (Grant ID: CC2214, Grant title: Elosegui-Artola CC2214) European Research Council (Grant ID: 851055 -VISCOMATRIX, Grant title: ERC 851055 - VISCOMATRIX)