The development of the Drosophila photoreceptor cells (R-cells) is uniquely suited to studying mechanisms of neuronal development. The development of these cells has been described in considerable detail. They are most abundant neuronal cell class in Drosophila which is an advantageous feature for molecular and developmental studies. The ability to stably introduce exogeneous genes into the Drosophila germline facititates an analysis of the factors which control neuron-specific gene expression. The isolation of mutations in genes encoding neuronal proteins can provide insight into their function. The earliest molecular feature so far described which distinguishes an R-cell specific pathway of neural development from all others is the expression of the gene encoding the protoreceptor cell specific glycoprotein, antigen 24B10 (Ag24B10). This antigen is a 160 kdal membrane glycoprotein which appears on developing R-cell bodies and axons at an early stage of development. We have cloned the gene encoding this protein (G24B10) and determined its chromosomal location. In this grant application we propose an analysis of the structure and developmental role of this protein. We will deduce the primary structure of the protein from the cDNA sequence, determine its structure at different developmental stages, analyze its membrane topology and isolate null mutations in the gene. These studies will provide clues to ag24B10's role in development and direct further studies toward unravelling its function. We will define the cis-acting factors determining R-cell specific expression using fusion genes containing the G24B10 promoter and the E. coli beta-galactosidase and Drosophila alcohol dehydrogenase structural genes. This information will be used to design an R-cell specific DNA vector for genetically engineering R-cells in an otherwise normal fly.
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