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

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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).