This proposal uses a newly discovered gene controlling multiple aspects of sexual behavior and neural development as an entry point to the dissection of the neurological, molecular and genetic mechanisms that generate of a set of complex behaviors in a higher organism. The dissatisfaction (dsf) gene of Drosophila controls appropriate sexual behavior in both males and females including sex partner choice, receptivity to courtship, copulation efficiency and egg laying behavior. It is also necessary for development of identified sex-specific neurons in both males and females. Genetic studies show that dsf defines a novel pathway that controls sexual differentiation of the nervous system but not of the cuticle. A combination of genetic, molecular, behavioral and neurological experiments will be used to investigate the mechanisms behind the generation of male- and female-specific behaviors. The structure and expression pattern of dsf will be used to gain insight into the mechanism by which dsf functions in the regulation of neural development. Studies of the temporal, spatial and sex-specific regulation of dsf function will be performed to understand integration of dsf into the general regulatory mechanisms functioning within the nervous system and into the genetic cascade which controls sexual development. The expression pattern of dsf and the projections of dsf-expressing cells will be mapped as part of the construction of a wiring diagram of the sex-specific nervous system. Various techniques will be used to study the specific defects that occur in both dsf-expressing and dsf-non-expressing cells in the absence of dsf function. A functional map of the sexual nervous system, both as it relates to general male and female behaviors and to the role of dsf, will be generated via the use of the regulatory sequences of dsf and other genes to target expression of potential key regulatory components to limited regions of the nervous system. Such """"""""genetic sex-changes"""""""" will be coupled to behavioral analysis of animals whose non-nervous system sexual differentiation is genetically locked in a male or female mode, thus eliminating complications arising from intersexual or abnormal cuticular development. Genetic screens for genes which functionally interact with dsf will be initiated.
