Although cell-cell interaction plays a key regulatory role in development, little is known about the underlying molecular mechanisms. The diverse cell types comprising the Drosophila retina appear to arise through cell- cell interactions. Lineage studies in the vertebrate nervous system allude to a similar mechanism of regulating cell fate. Due to its accessibility to molecular and classical genetic analysis, the Drosophila compound eye is well suited to the identification and molecular characterization of environmental cues regulating cell fate. A molecular genetic and biochemical analysis of the bride of sevenless (boss) gene is proposed. The expression of this gene is required in one developing cell, R8, for the development of only one of its seven neighbors, namely the R7 cell, suggesting that boss is required to produce a signal specifically controlling R7 development. Interestingly, expression of another gene, sevenless, is required in the R7 cell for its own development. The structure of the sevenless protein is similar to tyrosine kinase-like receptor proteins. These data have led to the hypothesis that the sevenless protein is a receptor which binds the boss protein produced by the R8 cell. To test this hypothesis we propose to: (i) clone and sequence the boss gene; (ii) biochemically characterize the boss gene product; (iii) prepare antibodies to boss to determine where and when the boss protein is expressed; (iv) overproduce the boss protein; and (v) test the ability of the boss protein to bind to the sevenless protein and thereby promote tyrosine phosphorylation. It is anticipated that the boss protein will represent a class of proteins found both invertebrates and vertebrates, including human, which regulate development. Mutations in the boss gene give rise to subtle developmental defects leading to behavioral abnormalities. An understanding of the role of similar genes in human may provide molecular insight into specific behavioral and developmental abnormalities.
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