Cadherins function in the developing zebrafish RGCs

描述（由申请人提供）：本研究的长期目标是确定协调和差异细胞粘附如何调节斑马鱼视觉系统的发育，特别强调钙粘蛋白细胞粘附分子在视网膜神经节细胞发育中的作用。钙粘蛋白是一种重要的细胞粘附分子，与包括神经系统在内的多种组织和器官的发育有关。使用多种脊椎动物物种的体外和体内研究都表明，钙粘蛋白参与视网膜轴突成束、轴突生长和寻路。然而，迄今为止，大多数研究都集中在钙粘蛋白-2（N-cadherin）上，而关于其他钙粘蛋白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，关于不同钙粘蛋白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和钙粘蛋白-4（R-cadherin）在斑马鱼视觉系统发育过程中的表达模式。本研究拟探讨钙粘蛋白-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。本研究有两个具体的目的：A）确定钙粘蛋白-4在斑马鱼视网膜神经节细胞发育中的功能，以及B）确定钙粘蛋白-2在斑马鱼视网膜神经节细胞发育中的功能，并将其在视网膜神经节细胞发育中的功能与钙粘蛋白-4进行比较。本项目将使用各种技术（例如，应用钙粘蛋白抗体、钙粘蛋白显性阴性构建体、检查钙粘蛋白-2突变体）。拟议的研究旨在揭示视网膜神经节细胞发育的潜在机制，可能为受伤或先天性缺陷的人类视网膜和视神经组织的治疗提供见解。

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.