Control of cortical actin assembly and cadherin‐catenin localization by GPCRs and RhoGTPases

Many common and permanently disabling human birth defects, such as spina bifida, are caused by the loss of cell shape changes and tissue movements in the early embryo. Therefore, it is important to understand how these cell shape changes are regulated during embryonic development. It has been shown previously that the actin cytoskeleton is required for normal tissue movements at these stages. Furthermore, the expression and localization of cadherin‐catenin complex are relevant for cell adhesion and F‐actin assembly and their lost can increase risk of metastasis in carcinomas and alter normal cell movements during embryonic development. Using the Xenopus laevis embryo as a model, we are currently investigating the mechanisms by which cortical actin assembly is regulated during development and the signaling pathways relevant for the cadherin‐catenin localization. We have identified two G‐protein couple receptors, a novel GPCR receptor termed xFlop and xLPA, and the small GTPase Rac1, as key molecules involved in this process. We have also shown that RhoF, another member of the Rho GTPases, is also involved in regulating actin cytoskeleton assembly in Xenopus laevis embryos. We hope this research could lead us to not only better understanding of cortical actin assembly and remodeling in early stages of Xenopus laevis embryos, but also to develop novel treatments for spina bifida and human cancer metastasis.