The neural and genetic substrates of sexual behavior in Drosophila.

fruitless (fru), originally identified with its mutant conferring male homosexuality, is a neural sex determination gene in Drosophila that produces sexually dimorphic sets of transcripts. In the nervous system, Fru is translated only in males. Fru proteins likely regulate the transcription of a set of downstream genes. The expression of Fru proteins is sufficient to induce male sexual behavior in females. A group of fru-expressing neurons called "mAL" neurons in the brain shows conspicuous sexual dimorphism. mAL is composed of 5 neurons in females and 30 neurons in males. It includes neurons with bilateral projections in males and contralateral projections in females. Terminal arborization patterns are also sexually dimorphic. These three characteristics are feminized in fru mutant males. The inactivation of cell death genes results in the production of additional mAL neurons that are of the male type in the female brain. This suggests that male-specific Fru inhibits mAL neuron death, leading to the formation of a male-specific neural circuit that underlies male sexual behavior. Fru orchestrates a spectrum of downstream genes as a master control gene to establish the maleness of the brain.