RHO AND GASTRULATION MOVEMENTS IN XENOPUS LAEVIS

本实验旨在确定Rho蛋白是否在爪蟾原肠胚形成过程中调节形态发生运动。初步结果表明，RhoA调节了原肠形成过程中发生的一种特定的细胞运动，即收敛-伸展运动。具体目标1中提出的实验将进一步研究这种可能性，确定内源性中胚层的会聚-伸展运动是否需要Rho蛋白的功能。特异性靶2号的实验将确定Rho激酶（将RhoA与肌动蛋白细胞骨架的调节联系起来）是否介导原肠胚形成过程中的会聚-伸展运动。最后，在Specific Aim number 3中的实验旨在分离非洲爪蟾RhoA同源物，并确定它们是否介导原肠胚形成过程中的收敛-伸展运动。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起着重要作用。Rho蛋白和Rho激酶已被证明在肿瘤形成、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为它们的活性如何在这些疾病中被调节提供进一步的线索。

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.