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

描述（由申请人提供）：本项目的长期目标是确定钙粘蛋白分子在脊椎动物视觉系统发育中的作用，特别强调视网膜。钙粘蛋白是一种重要的细胞粘附分子，与包括视觉系统在内的多种组织和器官的发育有关。人类的Usher综合征1F型（视觉和听觉缺陷）是由钙粘蛋白基因突变引起的。关于I型经典钙粘蛋白在脊椎动物视觉系统中的表达和功能有广泛的信息，但关于II型钙粘蛋白在视网膜发育中的功能还没有公开的报道。以斑马鱼为模型生物，我们最近研究了几种II型钙粘蛋白在发育中的视觉系统中的表达，并开始研究II型钙粘蛋白亚家族成员钙粘蛋白6在斑马鱼视网膜发育中的作用。本提案的具体目标是：1.验证斑马鱼视网膜神经节和无长突细胞的分化需要钙粘蛋白6功能的假设;和2.验证钙粘蛋白10参与斑马鱼视网膜神经节和无长突细胞发育的假说。本项目将采用多种技术（如吗啉代反义寡核苷酸技术、显性负性构建体应用、镶嵌分析）在视网膜细胞和组织水平研究钙粘蛋白功能。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，可能会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。拟议的研究将发生在一个部门，有一个证明承诺本科研究人员的发展。在过去的5年里，QL（PI）和RLL（合作研究者）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的学生的本科研究经验（通过直接参与拟议的实验），并扩大接触他们的研究经验，以数百名学生（通过向学生展示学生的研究数据在大型生物学导论类）。

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).