Non-muscle myosin II acts non-cell autonomously to guide collective migration of the zebrafish polster cells

Collective cell migration is crucial in embryonic development and tumour dissemination. How cell-cell interactions guide collective cell migration is partially understood with a growing body of evidence pointing to a role for mechanical signals and intercellular tension. During zebrafish gastrulation, the anterior axial mesendoderm, also called polster, migrates collectively towards the animal pole. We here investigate the role of non-muscle myosin II (NMII), a well-known generator of intracellular tension, in this migration and uncover an unexpected non-cell-autonomous function. Inhibiting NMII activity, via genetic or pharmacological approaches, impairs both the speed and orientation of polster cells. Transplant experiments show that while NMII is required within the polster for proper cell orientation, it is not required in a cell-autonomous manner. Instead, NMII activity in neighbouring cells is essential to orient a given cells protrusions. Mechanistically, NMII localizes to the rear of cells and the base of actin-rich protrusions, where it promotes F-actin retrograde flow and generates mechanical tension. Using a conformation-specific -catenin antibody, we show that NMII-dependent tension is required to open -catenin in adjacent cells, providing a direct mechanotransductive link between neighbouring cells. These findings suggest a model in which protrusions not only serve as locomotory structures, but also as physical conduits for directional cues via transmission of a mechanical signal. Actomyosin-based contractility in one cell influences polarity in its neighbour, thereby ensuring directional coherence of the migrating group.