The nervous system is comprised of a complex set of different neuronal cell types. The molecular mechanisms which control neuronal differentiation are unknown. The Drosophila eye provides an excellent model system for studying neuronal development. The eye contains a relatively simple set of cells in repeating units called ommatidia and the development of each cell type has been well characterized. These cells include the eight photoreceptor cells (R cells), three types of pigment cells, lens-secreting cone cells, and a nerve-bristle cell group. It has been shown that there is no strict cell lineage relationship between these cells, indicating that the differentiation of these cell types is dependent on cell-cell interactions in the developing eye imaginal disc. The focus of these studies will be to determine at the molecular level how these cell-cell interactions occur and result in the differentiation of cell types. Drosophila genetics provides a powerful tool for studying development. Mutants can be obtained which interrupt steps in a developmental pathway allowing the molecular characterization of these gene products. We have isolated a mutation, bride of sevenless (boss), which results in the absence of R 7, the last R cell to differentiate. We have performed mosaic analysis on boss and found that it is necessary in R 8, the first R cell to differentiate. It is not necessary in the cell affected, R 7. Another mutation, sevenless (sev), was isolated previously which also affects R 7 development. Unlike boss, sev is required in R 7 and is a receptor tyrosine kinase. We speculate that boss is required in R 8 to produce the signal received by R 7 through the sev receptor. The experiments described in this study will clarify the role R 8 plays in R 7 development . We will clone the boss gene and determine its coding and upstream promotor sequences using the efficient cloning techniques available in Drosophila such as chromosomal walking and P element """"""""tagging."""""""" The expression pattern in the eye imaginal disc will be analyzed using antibodies generated against the boss antigen. In addition, the appropriate boss promotor-reporter (lac Z) DNA constructs will be made and introduced into files as a confirmation of the antibody staining. Temperature sensitive mutations will be generated to test the necessary timing of expression of boss. The boss gene will be expressed in all developing disc cells and in subsets of disc cells by using the appropriate promotors to test the effect of inappropriate expression of boss in cells which do not normally express boss. A search for homologous genes in higher eucaryotes will be carried out to find genes with a similar function in the development of mammals.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Genetics Study Section (GEN)
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Albert Einstein College of Medicine
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