TY - JOUR T1 - RhoGAP RGA-8 supports morphogenesis in <em>C. elegans</em> by polarizing epithelia through CDC-42 JF - bioRxiv DO - 10.1101/2019.12.15.877332 SP - 2019.12.15.877332 AU - Hamidah Raduwan AU - Shashikala Sasidharan AU - Luigy Cordova Burgos AU - Andre G. Wallace AU - Martha C. Soto Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/12/16/2019.12.15.877332.abstract N2 - CDC-42 regulation of non-muscle myosin/NMY-2 is required for polarity maintenance in the one-cell embryo of C. elegans. CDC-42 and NMY-2 regulate polarity throughout embryogenesis, but their contribution to later events of morphogenesis are less understood. We have shown that epidermal enclosure requires the GTPase CED-10/Rac1 and WAVE/Scar complex, its effector, to promote protrusions that drive enclosure through the branch actin regulator Arp2/3. Our analysis here of RGA-8, a homolog of SH3BP1/Rich1/ARHGAP17/Nadrin, with BAR and RhoGAP motifs, suggests it regulates CDC-42, so that NMY-2 promotes two events of epidermal morphogenesis: ventral enclosure and elongation. Genetic and molecular data suggest RGA-8 regulates CDC-42, and the CDC-42 effectors WSP-1 and MRCK-1, in parallel to F-BAR proteins TOCA-1 and TOCA-2. The RGA-8-CDC-42-WSP-1 pathway enriches myosin in migrating epidermal cells during ventral enclosure. We propose TOCA proteins and RGA-8 use BAR domains to localize and regenerate CDC-42 activity, thus regulating F-actin levels, through the branched actin regulator WSP-1, and myosin polarity through the myosin kinase MRCK-1. Regulated CDC-42 thus polarizes epithelia, to control cell migrations and cell shape changes of embryonic morphogenesis.Summary RGA-8, a protein with membrane binding and actin regulatory motifs, promotes embryonic morphogenesis by localizing active CDC-42 in developing epithelia, thus controlling actin and actin motors during cell movements. ER -