Decoupling the Roles of Cell Shape and Mechanical Stress in Orienting and Cueing Epithelial Mitosis

Abstract

Summary: Distinct mechanisms involving cell shape and mechanical force are known to influence the rate and orientation of division in cultured cells. However, uncoupling the impact of shape and force in tissues remains challenging. Combining stretching of Xenopus tissue with mathematical methods of inferring relative mechanical stress, we find separate roles for cell shape and mechanical stress in orienting and cueing division. We demonstrate that division orientation is best predicted by an axis of cell shape defined by the position of tricellular junctions (TCJs), which align with local cell stress rather than tissue-level stress. The alignment of division to cell shape requires functional cadherin and the localization of the spindle orientation protein, LGN, to TCJs but is not sensitive to relative cell stress magnitude. In contrast, proliferation rate is more directly regulated by mechanical stress, being correlated with relative isotropic stress and decoupled from cell shape when myosin II is depleted. : Nestor-Bergmann et al. use whole-tissue stretching and mathematical modeling to dissect the roles of mechanical stress and cell shape in cell division. They show that division orientation in stretched tissue is regulated indirectly by changes in cell shape, while division rate is more directly regulated by mechanical stress. Keywords: cell division, mitosis, mitotic spindle, cell proliferation, vertex model, mechanical stress, cell shape, force, Xenopus, epithelium