Distinct Roles and Synergistic Function of Fru(M) Isoforms in Drosophila Olfactory Receptor Neurons.

Sexual dimorphism in Drosophila courtship circuits requires the male-specific transcription factor fru(M), which is alternatively spliced to encode the Fru(MA), Fru(MB), and Fru(MC) isoforms. Most fru(M)-positive neurons express multiple variants; however, the functional significance of their co-expression remains undetermined. Do co-expressed isoforms each play unique roles to jointly regulate dimorphism? By focusing on fru(M)-positive olfactory receptor neurons (ORNs), here, we show that Fru(MB) and Fru(MC) are both required for males' age-dependent sensitization to aphrodisiac olfactory cues in a cell-autonomous manner. Interestingly, Fru(MB) expression is upregulated with age in Or47b and Ir84a ORNs, and its overexpression mimics the effect of age in elevating olfactory responses. Mechanistically, Fru(MB) and Fru(MC) synergistically mediate response sensitization through cooperation of their respective downstream effectors, namely, PPK25 and PPK23, which are both required for forming a functional amplification channel in ORNs. Together, these results provide critical mechanistic insight into how co-expressed Fru(M) isoforms jointly coordinate dimorphic neurophysiology.