Hippo kinases maintain polarity during directional cell migration in Caenorhabditis elegans

Abstract

Precise positioning of cells is crucial for metazoan development. Despite immense progress in the elucidation of the attractive cues of cell migration, the repulsive mechanisms that prevent the formation of secondary leading edges remain less investigated. Here, we demonstrate that Caenorhabditis elegans Hippo kinases promote cell migration along the anterior–posterior body axis via the inhibition of dorsal–ventral ( DV ) migration. Ectopic DV polarization was also demonstrated in gain‐of‐function mutant animals for C. elegans RhoG MIG ‐2. We identified serine 139 of MIG ‐2 as a novel conserved Hippo kinase phosphorylation site and demonstrated that purified Hippo kinases directly phosphorylate MIG ‐2 S139 . Live imaging analysis of genome‐edited animals indicates that MIG ‐2 S139 phosphorylation impedes actin assembly in migrating cells. Intriguingly, Hippo kinases are excluded from the leading edge in wild‐type cells, while MIG ‐2 loss induces uniform distribution of Hippo kinases. We provide evidence that Hippo kinases inhibit RhoG activity locally and are in turn restricted to the cell body by RhoG‐mediated polarization. Therefore, we propose that the Hippo–RhoG feedback regulation maintains cell polarity during directional cell motility. image Directional cell migration in C. elegans requires reciprocal regulation between Hippo kinases and Rho GTP ase MIG ‐2 to ensure correct positioning of neural progenitors. Hippo kinases are crucial for directional cell migration in C. elegans . Hippo kinases maintain the anterior–posterior directional cell migration by inhibiting the ectopic dorsal–ventral migration. Hippo kinases directly phosphorylate C. elegans Rho GTP ase MIG ‐2 on a conserved serine 139. MIG ‐2 S139 phosphorylation impedes actin assembly in migrating cells. Hippo kinases are excluded from the leading edge by MIG ‐2‐mediated polarization.