In flies as in humans one of the most obvious differences between adults are the sex-specific behaviors involved in reproduction. The proposed research is directed at understanding the role of the fruitless (fru) gene in specifying components of Drosophila's sexual behavior and of its sexually -dimorphic internal anatomy. The phenotypic defects caused by fru mutations suggest that this gene is required for at least several of the later steps in the male courtship sequence. Preliminary studies-- involving molecular, behavioral, and neuroanatomical experiments--suggest that fru exerts its effect on sex-specific attributes of the fly's biology by acting as a factor that is part of the sex-determination hierarchy of gene actions (and their interactions) in Drosophila. Moreover, fru is unique, in that it appears to be the first gene known in a previously unrecognized branch of this hierarchy, which governs many (perhaps most) aspects of the male's sexual behavior. Other preliminary results, from analysis of enhancer-trapped transposons inserted at the fru genetic locus, imply that this gene (in its native form) is expressed in a limited number of cells in the adult central nervous system; and, furthermore, in a male-specific manner in many of these cells. A collaborative analysis is proposed that will make use of combined expertise in molecular genetics, developmental biology, neuroanatomy, and behavior, to address the role of fru in specifying the male-specific neural functions and neuromuscular structures that underlie important features of this organism's reproductive behavior. The studies will be carried out at a variety of levels: Identification of the fru gene products and analysis of how their production is regulated by the action of gene's located further up the hierarchy. Dissection of the regulatory sequences within the fru locus, regarding separate components of the gene's spatial and temporal expression patterns. Induction and phenotypic analysis of a fru-null mutant (if none exists among the extant cases). Analysis of possible interactions between fru and another gene within the sex-determination hierarchy. Delineation of cells in the CNS that express the fru mRNA and the native FRU protein, including the construction of a neuronal wiring diagram for such cells. Molecular and genetic-mosaic dissection of the phenotypic relevance of different CNS regions in which fru is expressed. Dissection of the phenotypic relevance of fru expression at different stages during development and in adulthood. Interspecific studies: molecular homologs; behavioral and neural experiments. Assessment of the adaptive significance of fru's action, as it relates to sex-specific behaviors and tissues.
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