Non-apical mitoses contribute to cell delamination during mouse gastrulation

International audience ; During the epithelial-mesenchymal transition driving mouse embryo gastrulation, cells divide more frequently at the primitive streak, and half of those divisions happen away from the apical pole. These observations suggest that non-apical mitoses might play a role in cell delamination. We aim to uncover and challenge the molecular determinants of mitosis position in different regions of the epiblast through computational modeling and pharmacological treatments of embryos and stem cell-based epiblast spheroids. Blocking basement membrane degradation at the streak has no impact on the asymmetry in mitosis frequency and position. By contrast, disturbance of the actomyosin cytoskeleton or cell cycle dynamics elicits ectopic non-apical mitosis and shows that the streak region is characterized by local relaxation of the actomyosin cytoskeleton and less stringent regulation of cell division. These factors are essential for normal dynamics at the streak and favor cell delamination from the epiblast. Epithelial-mesenchymal transition (EMT) is a reversible process by which a static epithelial cell becomes motile through the acquisition of a mesenchymal phenotype. It involves a loss or change in intercellular junctions, reorganization of the cytoskeleton, a switch from apicalbasal to front-rear polarity, and remodeling of the extracellular matrix 1,2 . EMT is a fluid non-linear spectrum in which cells can adopt intermediate phenotypes with various levels of epithelial and mesenchymal features 2 . Gastrulation, an evolutionary conserved developmental event through which multiple germ layers arise from a single epithelium, occurs through EMT-mediated cell delamination. In the mouse embryo, gastrulation takes place in the primitive streak (PS), a structure specified in the posterior region of the epiblast at embryonic day (E) 6 3 . One of the earliest steps of gastrulation EMT is the degradation of the epiblast basement membrane 4,5 . Perforations are already present globally before the onset of ...