A ratchet-like apical constriction drives cell ingression during the mouse gastrulation EMT

Abstract

Epithelial-to-Mesenchymal Transition (EMT) is a fundamental process in which epithelial cells acquire mesenchymal phenotypes and the ability to migrate. EMT is the hallmark of gastrulation, an evolutionarily conserved developmental process. In mammals, epiblast cells lose pluripotency and ingress at the primitive streak to form mesoderm. Cell exit from the epiblast epithelial layer and the associated EMT are dynamically regulated processes involving a stereotypical sequence of cell behaviors. 3D time-lapse imaging of gastrulating mouse embryos combined with cell and tissue scale data analyses revealed the stochastic-like ingression of epiblast cells at the primitive streak. Ingressing cells constrict their apical surfaces in a pulsed ratchet-like fashion through asynchronous shrinkage of apical junctions. A quantitative analyses of the distribution of apical proteins, revealed the anisotropic and complementary distribution of members of the actomyosin network and Crumbs2 complexes, potential regulators of asynchronous shrinkage of cell junctions. The analysis of mutants demonstrated a requirement for Crumbs2 in Myosin2 localization and activity at apical junctions, and as a candidate for regulating actomyosin anisotropy.