Cadherin6 and -10 Function in Retinal Ganglion and Amacrine Cell Development

描述(申请人提供)：这个项目的长期目标是确定钙粘附素分子在脊椎动物视觉系统发育中的作用，特别是视网膜。钙粘附素是重要的细胞黏附分子，参与包括视觉系统在内的多种组织和器官的发育。人类的1F型Usher综合征(视觉和听觉缺陷)是由于钙粘附素基因突变引起的。关于I型经典钙粘附素在脊椎动物视觉系统中的表达和功能已有广泛的研究，但关于II型钙粘附素在视网膜发育中的作用尚未见报道。以斑马鱼为模型生物，我们最近检测了几种II型钙粘附素在视觉系统发育中的表达，并开始研究II型钙粘附素亚家族成员钙粘蛋白6在斑马鱼视网膜发育中的作用。目前建议的具体目的是：1.检验斑马鱼视网膜神经节和无长突细胞分化需要钙粘蛋白6功能的假说；2.检验钙粘蛋白10参与斑马鱼视网膜神经节和无长突细胞发育的假说。该项目将采用多种技术(如吗啡反义寡核苷酸技术、显性负性结构的应用、镶嵌分析)在视网膜细胞和组织水平上研究钙粘附素的功能。这项拟议的研究旨在揭示脊椎动物视网膜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。这项拟议的研究将在一个致力于培养本科生研究人员的部门进行。在过去的5年里，QL(PI)和RLL(Co-Investigator)总共指导了35个本科生研究项目。在这里，我们建议加强和深化选定学生的本科生研究经验(通过直接参与建议的实验)，并扩大他们对数百名学生的研究经验的接触(通过在大型生物学入门课上向学生展示学生的研究数据)。

DESCRIPTION (provided by applicant): The long-term objectives of this project are to determine the roles of cadherin molecules in the development of vertebrate visual system, with special emphasis on the retina. Cadherins are important cell adhesion molecules that have been implicated in the development of a variety of tissues and organs including the visual system. Usher syndrome type 1F in humans (visual and auditory defects) is due to mutations in a cadherin gene. There is extensive information on expression and function of type I classic cadherins in the vertebrate visual system, but there is no published report on type II cadherins function in retinal development. Using zebrafish as our model organism, we recently examined several type II cadherins expression in developing visual system and have begun to study the role of cadherin6, a member of the type II cadherin subfamily, in zebrafish retinal development. The specific aims of the current proposal are: 1. to test the hypothesis that differentiation of zebrafish retinal ganglion and amacrine cells require cadherin6 function; and 2. To test the hypothesis that cadherin10 is involved in zebrafish retinal ganglion and amacrine cells development. A variety of techniques (e.g. morpholino antisense oligonucleotides technique, application of dominant negative construct, mosaic analysis) will be employed in the project to study cadherin function at both the retinal cell and tissue levels. The proposed studies, designed to uncover mechanisms underlying vertebrate retinal cell development, may provide insights into therapies for injured or congenitally defective human retinal and optic nerve tissues. The proposed research will take place in a department that has a demonstrated commitment to development of undergraduate researchers. In the last 5 years, QL (PI) and RLL (Co- investigator) have mentored a total of 35 undergraduate research projects. Here we propose to strengthen and deepen the undergraduate research experience for selected students (by direct involvement in the proposed experiments), and to broaden the exposure to their research experience to hundreds of students (by presenting the students' research data to students in large Introductory Biology classes).