Regulation of cell shape and mechanics by Rho GEFs and GAPs in a proliferative epithelial tissue

Epithelial cell shape results from the combination of intrinsic properties of the actomyosin cytoskeleton and extrinsic properties due to physical interactions with neighbouring cells, in particular at the adherens junctions. In the Drosophila epidermis, non-muscle myosin type II (MyoII) is a key force regulator for the control of cell shape. MyoII is activated by Rho GTPases, themselves activated by guanine nucleotide exchange factors (GEFs) and inhibited by GTPase-activating proteins (GAPs). Here, we screened 28 Drosophila GAPs and 36 GEFs on the pupal notum to identify regulators of MyoII distribution and dynamics, epithelial cell shape and cytokinesis. Among the candidates identified, we show that PlexA, a transmembrane GAP, regulates the shape of sensory organ precursors in a cell-autonomous manner, and that RhoGEF Cyst acts downstream of Crumbs and trimeric G proteins Gβ13F and Gγ1 to regulate junctional MyoII and adherens junction remodelling during interphase and cytokinesis, in a non-cell-autonomous manner. This study provides a comprehensive description of the impact of GEFs and GAPs on epithelial homeostasis, and sheds light on the mechanisms linking actomyosin contractility, cell shape regulation and cell junction dynamics.