RhoGTPases in Early Eye Development

描述（由申请人提供）：本申请的长期目标是了解早期眼睛发育的机制。更具体地说，我们希望了解肌动蛋白调节gtpase如何影响晶状体和视网膜上皮的协调形态发生。Rho家族gtpase是本应用的重点，作为调节细胞内信号传导的分子开关。它们在许多不同的功能中发挥作用，但在调节肌动蛋白重排，从而调节细胞形状，细胞迁移和细胞突起的产生方面具有突出作用。它们还能影响细胞存活。我们4月初旨在调查其功能的眼睛轮廓形态发生:(1)确定Cdc42 Rac1功能在一个级联调节镜头泡关闭和分离,(2)确定是否删除Cdc42早期,Rac1或者RhoA给一个缺陷在镜头坑凹入,(3)确定光学镜头坑内陷囊泡有主导作用,和(4)确定FGF信号通路的调节活动Rac1, Cdc42或RhoA通路。这种应用对人类健康具有直接意义，因为Rho家族GTPases与包括癌症在内的多种人类疾病有关。gtpase参与癌症的病因学源于它们调节细胞粘附、细胞迁移和细胞存活的能力。我们将要研究的上皮内陷的过程在很多方面类似于侵袭性癌症的侵袭过程。由于这个原因，这个项目可能对癌症治疗有启示。

DESCRIPTION (provided by applicant): The long-term goal of this application is an understanding of the mechanisms of early eye development. More specifically, we wish to understand how actin-modulating GTPases influence the coordinated morphogenesis of the lens and retinal epithelium. The Rho family GTPases that are the focus of this application act as molecular switches that regulate signaling within the cell. They function in many different capacities, but have a prominent role in the regulation of actin rearrangement and consequently, the regulation of cell shape, cell migration and the generation of cellular protrusions. They can also influence cell survival. We outline 4 aims to investigate their function in early eye morphogenesis: (1) To determine whether Cdc42 and Rac1 function in a cascade to regulate lens vesicle closure and separation, (2) To determine whether early deletion of Cdc42, Rac1 or RhoA gives a defect in lens pit invagination, (3) To determine whether the optic vesicle has a dominant role in lens pit invagination, and (4) To determine whether the FGF signaling pathway modulates activity of the Rac1, Cdc42 or RhoA pathways. This application has direct significance to human health because the Rho family GTPases are implicated in a variety of human disease including cancer. The involvement of the GTPases in the etiology of cancer is derived from their ability to regulate cell adhesion, cell migration and cell survival. The process of epithelial invagination that we will study is in many ways analogous to the process of invasion that accompanies the development of aggressive cancers. For this reasop, this project may have implications for cancer therapy.