The aim of the research proposed is to understand the developmental mechanisms by which the cells of the retina achieve their specialized sub- types. glass mutations specifically remove the photoreceptor neurons of the Drosophila visual system; these cells begin to develop as neurons but fail to express photoreceptor specific genes, and later die. glass encodes a protein with five Zinc-finger domains; such proteins have been shown in other organisms to act as transcription factors. Thus glass may act directly to regulate photoreceptor cell-specific gene expression. We have shown that the glass protein binds in-vitro to sequences from enhancer elements of one such gene (a rhodopsin). glass is expressed in all the cells of the developing retina, but it is only active in the developing photoreceptors (by showing the effect on a reporter gene of glass DNA binding sites). Thus the regulation of glass activity is critical for photoreceptor cell development and this occurs at two levels: at transcription, and after translation (by incoming positional signals). To pursue this dual regulation we will conduct two projects: 1) To understand glass transcriptional regulation we will undertake a functional analysis of the glass gene promoter by mutational studies, and 2) To identify novel genes that interact with glass we will use a series of genetic screens and the first will be for dominant enhancers and suppressors of weak glass alleles. Preliminary screens have successfully tested the feasibility of this approach (we have recovered three such mutations). Once isolated we will characterize the effects of our novel mutations and in the long term, clone the genes responsible to study their molecular functions.
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