Protocadherin-17 and -9 Function in Retinal 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. Mutations in protocadherins (pcdhs) cause humans diseases including epilepsy, mental retardation and Usher syndrome (visual and/or auditory defects). There is extensive information on function of classic cadherins (e.g. N-cadherin and R- cadherin, also called cadherin-2 and cadherin-4, respectively) in the vertebrate visual system, but little is known about other cadherins including the pcdhs function in retinal development, and there is no published reports on pcdh17 and pcdh9 function in the development of the vertebrate visual system. Using zebrafish as our model organism, we recently examined pcdh17 and pcdh9 expression in developing visual system and have begun to study the role of pcdh17 in zebrafish retinal development. The specific aims of the current proposal are: 1. to test the hypothesis that differentiation of retinal cells requires pcdh17 function; and 2. to test the hypothesis that pcdh9 is involved in RGCs differentiation and pathfinding. A variety of techniques including morpholino antisense oligonucleotides technique, pcdh overexpression, proteomics, DNA microarray, will be employed in the project to study pcdhs function in retinal development. 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 the development of undergraduate researchers. We propose to strengthen and deepen the undergraduate research experience and to broaden the exposure to their research experience. We will significantly enhance hands-on research experience for students enrolled in the laboratory component of Cell Physiology, Developmental Biology, Neurobiology and Vertebrate Embryology (through their participating in aspects of the proposed experiments). We will also solicit proposals from students to apply for summer fellowships, where they can pursue their original research (centered on the themes in this proposal). These students will then present their research to other undergraduates at local or regional undergraduate and graduate students' research symposiums. PUBLIC HEALTH RELEVANCE: The proposed studies, designed to uncover mechanisms underlying vertebrate retinal cells differentiation, may provide insights into therapies for injured or congenitally defective human retinal and optic nerve tissues.