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The  fruitless  ( fru ) gene of  Drosophila melanogaster  generates two groups of protein products, the male-specific FruM proteins and non-sex-specific FruCOM proteins. The FruM proteins have a 101 amino acids (a.a.)-long extension at the N-terminus which is absent from FruCOM. We suggest that this N-terminal extension might confer male-specific roles on FruM interaction partner proteins such as Lola, which otherwise operates as a transcription factor common to both sexes. FruM-expressing neurons are known to connect with other neurons to form a sexually dimorphic circuit for male mating behavior. We propose that FruM proteins expressed in two synaptic partners specify, at the transcriptional level, signaling pathways through which select pre- and post-synaptic partners communicate, and thereby pleiotropic ligand-receptor pairs for cell-cell interactions acquire the high specificity for mutual connections between two FruM-positive cells. We further discuss the possibility that synaptic connections made by FruM-positive neurons are regulated by neural activities, which in turn upregulate Fru expression in active cells, resulting in feedforward enhancement of courtship activities of the male fly.

Sex Mysteries of the Fly Courtship Master Regulator Fruitless