Decoupling the roles of cell shape and mechanical stress in orienting and cueing epithelial mitosis

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 aligns with local cell stress rather than tissue-level stress. The alignment of division to cell shape requires functional cadherin and the localisation 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.