Basal cell extrusion primes pluripotent cells for differentiation

The blueprint of the mammalian body plan is laid out during gastrulation, when a trilaminar embryo is formed. This process entails a burst of embryonic cell proliferation, the ingression of pluripotent epithelial cells at the primitive streak, and their priming towards primitive streak fates. How these different events are coordinated remains unknown. Here, we developed a 3D culture of self-renewing pluripotent and epithelial cells that recapitulates the transcriptional and architectural features of the gastrulating mouse embryo. Using this system in combination with microfabrication and in vivo experiments, we found that proliferation triggers basal extrusion in cells that express high levels of the apical polarity protein aPKC. Upon extrusion, cells are more sensitive to Bmp, Wnt, and Nodal signaling, and upregulate the expression of primitive streak markers. This mechanistic coupling between cell position and gene expression ensures that the right cell types become specified at the right place during embryonic development.