CELL ADHESION FUNCTION IN THE VISUAL SYSTEM

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DESCRIPTION (provided by applicant): Numerous cadherin family members are expressed in the nervous system. Cadherins are well positioned to be important regulators of growth cone migration, fasciculation, defasciculation and target cell recognition during development. Various studies have established that cadherins are necessary for morphoregulatory processes during development, and cadherins were previously shown to regulate retinotectal projection. To understand how cadherin-mediated cell-cell adhesion controls differentiation and morphoregulatory movements during eye development, we will isolate cadherin cell adhesion molecules that are expressed in the developing visual system and determine spatial and temporal expression patterns for cadherins with particular attention to morphogenesis of the visual system. The zebrafish model system will be used to study cadherin function and regulation due to the advantages provided by the ease of experimental manipulation and genetic manipulation of developmental pathways. Experiments are proposed to examine functions for cadherin cell adhesion in the developing visual system. Cadherins are hypothesized to provide a combinatorial code for the wiring of various circuits in the nervous system. Connectivity within retina, retinofugal projections and tectofugal projections may be controlled by cadherin adhesion. Detailed examination of cadherin expression during development should provide significant insight into processes that establish connectivity with the visual system. Finally, we proposed to experimentally manipulate cadherin expression and function, and then examine the consequences on neuronal circuits in the visual system, particularly the retinotectal connections that form the retinotopic map in the optic tectum.