Cadherins modulate the self-organizing potential of gastruloids

Author:

Mayran AlexandreORCID,Kolly DominiqueORCID,Lopez-Delisle LucilleORCID,Romaniuk YuliiaORCID,Leonardi Maxine,Cossy Anne-CatherineORCID,Lacroix Theo,Amândio Ana Rita,Osteil PierreORCID,Duboule DenisORCID

Abstract

ABSTRACTGastruloids have recently emerged as an efficient four-dimensional model for studying some aspects of post-implantation embryonic patterning. They undergo gastrulation-like processes leading to the self-organization into highly reproducible biological objects. Here, we sought to uncover the molecular and cellular mechanism underlying this remarkable property. We report that self-organization competence is associated with a cell-specific coordination of a Cadherin switch. We find that N-Cadherin hinders gastruloids morphogenetic competence, for its inactivation leads to the formation of trunk-like structures in absence of extra-cellular matrix analogues. In contrast,E-Cadherinrepression bySnai1is critical for self-organization:Snai1establishes a cell-specific repressive pace by triggering the repression of a pluripotency-associated transcription program and its chromatin landscape, thus allowing a proper transition from E-to N-Cadherin to occur. Altogether, this work establishes a molecular mechanism that integrates the exit from pluripotency and the pace of cell differentiation, leading to the observed self-organizing potential of gastruloids.

Publisher

Cold Spring Harbor Laboratory

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