Rho1 functions through multiple effectors for proper epithelial wound repair. Travis K Rahe, Jeffrey M Verboon, Susan M Parkhurst. Division of Basic Sciences, Fred Hutchinson Cancer Research Institute, Seattle, WA.

   Epithelial wound repair in embryos is essential for the maintaining of an external environmental barrier, tissue integrity, and survival. One family of proteins, the Rho family of GTPases, have been found to play a vital role in the epithelial wound repair process. The Rho family of GTPases interact with numerous effectors in their GTP bound form to regulate actin and microtubule cytoskeletal reorganization. We find that Rho1 is required at every step of the epithelial wound healing process. We generated transgenic lines containing a series of substitution and point mutations that disrupt the functional and known protein binding domains of Rho1. Embryos expressing these various Rho1 mutations, as well as fluorescent markers, were laser wounded. We quantitatively assessed actin and microtubule machineries in cell orientation, migration, and adhesion during the repair process. We find that specific Rho1 effectors and/or molecular pathways are required at different steps in the wound healing process. We are currently investigating mutations in the effectors downstream of the relevant point mutations to integrate the Rho1 pathways required for the repair process. By establishing these effector pathways we are elucidating the role of Rho1 in the wound repair process, as well as gaining further insight into roles Rho1 may play in the developing organism.