Cadherins function in the developing zebrafish RGCs

描述(申请人提供)：这项研究的长期目标是确定协调和不同的细胞黏附如何调节斑马鱼视觉系统的发育，特别强调钙粘附素细胞黏附分子在视网膜神经节细胞发育中的作用。钙粘附素是一种重要的细胞黏附分子，参与了包括神经系统在内的多种组织器官的发育。在体外和体内对多种脊椎动物的研究表明，钙粘附素参与了视网膜轴突的颤动、轴突的生长和发病过程。然而，到目前为止，大多数研究都集中在钙粘蛋白-2(N-钙粘蛋白)上，而关于其他钙粘附素在这些过程中的作用，特别是体内功能的信息相对较少。此外，对不同钙粘附素在视网膜神经节细胞发育中的相对作用知之甚少。我们研究了钙粘蛋白-2和钙粘附素-4(R-钙粘蛋白)在斑马鱼发育过程中视觉系统的表达模式。我建议研究钙粘蛋白-2和钙粘蛋白-4在斑马鱼视网膜神经节细胞发育中的作用。本研究有两个具体目的：一是确定钙粘蛋白-4在斑马鱼视网膜神经节细胞发育中的作用；二是确定钙粘蛋白-2在斑马鱼视网膜神经节细胞发育中的作用，并将其与钙粘蛋白-4在视网膜神经节细胞发育中的作用进行比较。该项目将使用多种技术(例如，钙粘蛋白抗体的应用、钙粘蛋白显性-阴性结构、钙粘蛋白-2突变的检测)。这项拟议的研究旨在揭示视网膜神经节细胞发育的潜在机制，可能为治疗受损或先天缺陷的人类视网膜和视神经组织提供见解。

DESCRIPTION (provided by applicant): The long-term objective of this research is to determine how coordinated and differential cell adhesion regulates the development of the zebrafish visual system, with special emphasis on the role of cadherin cell adhesion molecules in the development of retinal ganglion cells. Cadherins are important cell adhesion molecules that have been implicated in the development of a variety of tissues and organs including the nervous system. Both in vitro and in vivo studies using a variety of vertebrate species have shown that cadherins are involved in retinal axon fasciculation, axonal outgrowth and pathfinding. However, most of the studies to date have focused on cadherin-2 (N-cadherin), and there is relatively little information on the roles, and in particular the in vivo functions, of other cadherins, in these processes. Moreover, little is known about relative roles of different cadherins in the development of retinal ganglion cells. We have studied expression patterns of both cadherin-2 and cadherin-4 (R-cadherin) in the visual system of developing zebrafish. I propose to study cadherin-2 and cadherin-4 function in zebrafish retinal ganglion cell development. This proposal has two specific aims: A) determine function of cadherin-4 in the development of zebrafish retinal ganglion cells, and B) determine function of cadherin-2 in the development of zebrafish retinal ganglion cells, and compare its function in retinal ganglion cell development with cadherin-4. A variety of techniques (e.g. application of cadherin antibodies, cadherin dominant-negative constructs, examination of cadherin-2 mutant) will be used in the project. The proposed studies, designed to uncover mechanisms underlying retinal ganglion cell development, may provide insights into therapies for injured or congenitally defective human retinal and optic nerve tissues.