DESCRIPTION (provided by applicant): Understanding the way in which a nervous system develops and is arranged to generate complex behaviors is a critical issue for neuroscience, with substantial connections to understanding neurological diseases and potential impact on mental health issues. Innate behaviors of Drosophila are both complex and amenable to study via a number of approaches including genetics, molecular biology, neuroanatomy, biochemistry, and cell biology. Sexual behavior is particularly amenable as there are multiple different male and female behaviors and neural or neuromuscular connections involved in courtship, mating and fertility, with individuals expressing only the male set of traits or the female set. Mutations that alter sexual behavior in males, females or both have been identified and characterized separately. Although some functions might be simplistically described as controlling body or mind, recent work shows that these genes function in a regulatory switch system with interactions at multiple levels. This network will be addressed as a system, with focus on the nature of the network and interactions within it. The behavioral, neural and regulatory network controlling sexual behavior and sex-specific neural development will be dissected with respect to four genes: retained, dissatisfaction, and the known sex- switch genes fruitless and doublesex. Each of these encodes a protein or proteins that act as transcriptional regulators with high similarity to proteins found in humans. The array of behavioral abnormalities associated with mutations in each gene will be examined with special emphasis on interactions between the functions of one gene and functions of others in the behavioral network. Expression patterns in both sexes for each gene and overlaps between genes will be determined. Targeted knock down of each gene will be used to map particular behaviors to cells co- expressing factors and to cells expressing only one factor. The mechanism of action of dissatisfaction, including the way it changes function in response to fruitless activity will be studied. Key tests involve possible repression or activating functions in one or both sexes, direct interaction with male fruitless proteins, and activation by a fruitless induced dissatisfaction ligand. PUBLIC HEALTH RELEVANCE: Formation and continued function of a nervous system capable of complex functions, integration of outside inputs, decision-making, and coordination with motor functions is critical for a healthy, happy and productive life. A neural-genetic network composed of four genes, all of which have homologues in humans, and the neurons in which they act having all the features mentioned above will be studied. Special emphasis will be placed on activities of each of the genes, their interactions, interactions of the cells involved, and possible hormonal contributions to behavior, allowing potential critical connections to similar functions in humans.