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.
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