Cadherins modulate the self-organizing potential of gastruloids

Abstract

Gastruloids 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.

CTCF-DEPENDENT INSULATION OFHoxb13AND THE HETEROCHRONIC CONTROL OF TAIL LENGTH

“…scRNA-seq. scRNA-seq of gastruloids at 144h were performed as in (61), with 10x Chemistry v3 as well as the analysis up to matrix generation. Then, analysis was performed using Seurat v4.3 (62) with R version 4.3.0.…”