ECM-integrin signalling instructs cellular position-sensing to pattern the early mouse embryo

Abstract

Development entails patterned emergence of diverse cell types within the embryo. In mammals, cells positioned inside the embryo gives rise to the inner cell mass (ICM) that eventually forms the embryo proper. Yet the molecular basis of how these cells recognise their inside position to instruct their fate is unknown. Here we show that cells perceive their position through extracellular matrix (ECM) and integrin-mediated adhesion. Provision of ECM to isolated embryonic cells induces ICM specification and alters subsequent spatial arrangement between epiblast (EPI) and primitive endoderm (PrE) cells that emerge within the ICM. Notably, this effect is dependent on integrin β 1 activity and involves apical to basal conversion of cell polarity. We demonstrate that ECM-integrin activity is sufficient for inside positional signalling and it is required for proper sorting of EPI/PrE cells. Our findings thus highlight the significance of ECM-integrin adhesion in enabling position-sensing by cells to achieve tissue patterning.

Adherens junctions stimulate and spatially guide integrin activation and extracellular matrix deposition

“…The most striking example of this is the basal region of the deep cells of the Xenopus animal cap, where integrin receptors are nearly absent prior to FN deposition, with b1 mainly concentrated at the lateral regions colocalizing with cadherins and relocalizing to the basal region after ECM deposition. Similarly, a recent publication revealed that, in the preimplantation mouse, integrin b1 is restricted to the cell-cell boundaries of the early blastocyst and absent from areas facing the lumen prior to the establishment of apicobasal polarity (Kim et al, 2021). The influence of AJs on ECM deposition and BM assembly is demonstrated in the BCR of Xenopus embryos, where the first fibrils form at the cell-cell boundary.…”