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In  Drosophila melanogaster , genes of the sex-determination hierarchy orchestrate the development and differentiation of sex-specific tissues, establishing sex-specific physiology and neural circuitry. One of these sex-determination genes,  fruitless  ( fru ), plays a key role in the formation of neural circuits underlying  Drosophila  male courtship behavior. Conservation of  fru  gene structure and sex-specific expression has been found in several insect orders, though it is still to be determined whether a male courtship role for the gene is employed in these species due to the lack of mutants and homologous experimental evidence. We have isolated the  fru  ortholog ( Md-fru ) from the common housefly,  Musca domestica , and show the gene’s conserved genomic structure. We demonstrate that male-specific  Md-fru  transcripts arise by conserved mechanisms of sex-specific splicing. Here we show that  Md-fru , is similarly involved in controlling male courtship behavior. A male courtship behavioral function for  Md-fru  was revealed by the behavioral and neuroanatomical analyses of a hypomorphic allele,  Md-tra man  , which specifically disrupted the expression of  Md-fru  in males, leading to severely impaired male courtship behavior. In line with a role in nervous system development, we found that expression of  Md-fru  was confined to neural tissues in the brain, most prominently in optic neuropil and in peripheral sensory organs. We propose that, like in  Drosophila , overt sexual differentiation of the housefly depends on a sex-determining pathway that bifurcates downstream of the  Md-tra  gene to coordinate dimorphic development of non-neuronal tissues mediated by  Md-dsx  with that of neuronal tissues largely mediated by  Md-fru .

Genetic Control of Courtship Behavior in the Housefly: Evidence for a Conserved Bifurcation of the Sex-Determining Pathway