CADHERIN MEDIATED PHOTORECEPTOR DIFFERENTIATION

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The long range objectives of this project are to determine the role of cellular interactions in regulating neuronal commitment and differentiation during development and regeneration of the teleost neural retina, with special emphasis on photoreceptors. The focus of the research plan is on specialized cell-cell junctions and the calcium- dependent adhesion molecules, cadherins, as mediators of inductive signalling events. Fusion proteins produced from zebrafish N-cadherin cDNA will be used to generate polyclonal antibodies capable of blocking cadherin-mediated cell-cell adhesion. The hypothesis is that cadherins/adherens junctions play a role in mediating choice of photoreceptor fate. Cadherin-specific blocking antibodies, fusion proteins, N-terminal fragments, or synthetic peptides, are applied to whole embryonic eyes in organ culture, and production of photoreceptors is monitored with rod-specific and cone-specific monoclonal antibodies and with in situ hybridization using isotype-specific rod and cone opsin riboprobes. Since abnormal cadherin function has been implicated in cellular transformation and metaplasia, a better understanding of the role of cadherins in regulating normal cell phenotype is of interest.