Cadherin mediated F-actin assembly and the regulation of morphogenetic movements during Xenopus laevis development.

摘要

As vertebrates, our basic body shape is governed by our bony skeletal system. However, during embryonic development, before our skeletal system appears, the overall shape of the embryo is controlled by the cytoskeleton of individual cells that control cell shape changes and tissue movements. In my thesis I show that cadherins are the site of actin assembly.;Firstly, I show that cell surface expression of C-cadherin is the rate-limiting step in cortical actin assembly and requires the binding of p120 catenin to the juxta membrane domain to assemble F-actin. Furthermore, cell surface expression of C-cadherin is regulated by at least two G protein-coupled receptors, Xflop, and LPA.;Secondly, I show that N-cadherin mediated actin assembly is required for apical constriction of the neural plate cells to form the neural tube, while E-cadherin mediated f-actin assembly is required for intercalation movements of the presumptive epidermis. In these tissues, N- and E-cadherin have unique sub-cellular localization patterns and cannot replace one another to assemble F-actin. However, in the pluripotent animal cap cells of the blastula, C-cadherin can be replaced by either N-, or E-cadherin, and all three classical cadherins can assemble F-actin.;Thirdly, I dissect out the function of the cadherin intracellular domain and show that the two different sub-domains control different aspects of this essential pathway. The catenin binding domain is required for cadherin expression, whilst the juxta membrane domain is required for actin assembly.