RHO AND GASTRULATION MOVEMENTS IN XENOPUS LAEVIS

这项提议中的实验旨在确定Rho蛋白是否调节非洲爪哇原肠发育过程中的形态发生运动。初步结果表明，RhoA调节原肠形成、会聚-伸展运动过程中发生的特定细胞运动。在特定目标1中提出的实验将通过确定体外内源性中胚层的会聚-延伸运动是否需要Rho蛋白功能来进一步研究这种可能性。在特定目标2中的实验将确定将RhoA与肌动蛋白细胞骨架调节联系在一起的Rho激酶是否在原肠形成过程中调节会聚-延伸运动。最后，在特定目标编号3的实验被设计来分离非洲爪哇RhoA同系物，并确定它们是否在原肠发育过程中调节会聚-延伸运动。这些实验对人类健康很重要，因为Rho蛋白在人类疾病的细胞运动中扮演着重要的角色。Rho蛋白和Rho激酶已被证明在肿瘤的形成、转移和高血压中起关键作用。因此，对这些分子在发育过程中的体内作用的研究可能会为这些疾病中如何调节它们的活性提供进一步的线索。

Experiments in this proposal are designed to determine if Rho proteins regulate morphogenic movements during Xenopus gastrulation. The preliminary results presented suggest that RhoA regulates a specific cell movement which occurs during gastrulation, convergent-extension movements. Experiments proposed in Specific Aim number 1 will further investigate this possibility by determining if convergent-extension movements of endogenous mesoderm in vitro require Rho protein function. Experiments in Specific Aim number 2 will determine if Rho kinases, which links RhoA to regulation of the actin cytoskeleton, mediate convergent-extension movements during gastrulation. Finally, experiments in Specific Aim number 3 are design to isolate Xenopus RhoA homologues and determine if they mediate convergent-extension movements during gastrulation. These experiments are important to human health because of the role that Rho proteins play in cell movements in human disease. Rho proteins and Rho kinase have been shown to play a pivotal role in tumor formation, metatasis and in hypertension. Therefore, a study of the in vivo role of these molecules during development may provide further clues as to how their activity may be regulated in these diseases.