Distinct Roles and Synergistic Function of FruM Isoforms in Drosophila Olfactory Receptor Neurons

Sexual dimorphism in Drosophila courtship circuits requires the male-specific transcription factor fruM, which is alternatively spliced to encode the FruMA, FruMB, and FruMC isoforms. Most fruM-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 fruM-positive olfactory receptor neurons (ORNs), here, we show that FruMB and FruMC are both required for males’ age-dependent sensitization to aphrodisiac olfactory cues in a cell-autonomous manner. Interestingly, FruMB expression is upregulated with age in Or47b and Ir84a ORNs, and its overexpression mimics the effect of age in elevating olfactory responses. Mechanistically, FruMB and FruMC 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 FruM isoforms jointly coordinate dimorphic neurophysiology. [Display omitted] •FruMB and FruMC are required for age-dependent sensitization in male ORN subsets•FruMB expression is selectively upregulated with age in male Or47b and Ir84a ORNs•FruMB overexpression in male Or47b and Ir84a ORNs confers response sensitization•Sensitization requires PPK25 and PPK23, respective targets for FruMB and FruMC Zhang et al. show how co-expressed FruM isoforms mediate male-specific neurophysiology. In the courtship-promoting Or47b and Ir84a olfactory receptor neurons (ORNs), both FruMB and FruMC are required for the neurons’ age-dependent response sensitization. Functional synergy arises from co-expression of FruMB and FruMC through cooperation of their respective downstream targets.