Roles of Rho small GTPase in zebrafish development

Abstract

RhoA small GTPase, as a key regulator for actin cytoskeletal rearrangement, plays pivotal roles during morphogenesis, cytokinesis, phagocytosis and cell migration, but little is known about its signaling mechanism that controls cell movement and cell survival in vivo. Using zebrafish as a model and a combination of gene suppression, functional rescue experiments together with specific pharmacological inhibitors, we demonstrate that RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements during zebrafish gastrulation, and it elicits such effect via two effectors, Rho kinase and Dia. In addition, RhoA also prevents apoptosis by activation of Mek/Erk pathway and upregulation of bcl-2 expression during zebrafish embryogenesis. Taken together, our study not only reveals the importance of RhoA in cell movement and cell survival during embryogenesis, but also demonstrates the suitability of zebrafish for studying signaling mechanism of various classes of small GTPases in regulating cell dynamics in vivo.