Interphase cell morphology defines the mode, symmetry, and outcome of mitosis

Abstract

During tissue formation, dynamic cell shape changes drive morphogenesis while asymmetric divisions create cellular diversity. We found that the shifts in cell morphology that shape tissues could concomitantly act as conserved instructive cues that trigger asymmetric division and direct core identity decisions underpinning tissue building. We performed single-cell morphometric analyses of endothelial and other mesenchymal-like cells. Distinct morphological changes switched cells to an "isomorphic" mode of division, which preserved pre-mitotic morphology throughout mitosis. In isomorphic divisions, interphase morphology appeared to provide a geometric code defining mitotic symmetry, fate determinant partitioning, and daughter state. Rab4-positive endosomes recognized this code, allowing them to respond to pre-mitotic morphology and segregate determinants accordingly. Thus, morphogenetic shape change sculpts tissue form while also generating cellular heterogeneity, thereby driving tissue assembly.