Combinatorial Contact Cues Specify Cell Division Orientation by Directing Cortical Myosin Flows.

Cell division axes during development are specified in different orientations to establish multicellular assemblies, but the mechanisms that generate division axis diversity remain unclear. We show here that patterns of cell contact provide cues that diversify cell division orientation by modulating cortical non-muscle myosin flow. We reconstituted in vivo contact patterns using beads or isolated cells to show two findings. First, we identified three contact-dependent cues that pattern cell division orientation and myosin flow: physical contact, contact asymmetry, and a Wnt signal. Second, we experimentally demonstrated that myosin flow generates forces that trigger plasma membrane movements and propose that their anisotropy drives cell division orientation. Our data suggest that contact-dependent control of myosin specifies the division axes of Caenorhabditis elegans AB, ABa, EMS cells, and the mouse AB cell. The contact pattern-dependent generation of myosin flows, in concert with known microtubule/dynein pathways, may greatly expand division axis diversity during development.