Integrating lipid metabolism, pheromone production and perception by Fruitless and Hepatocyte nuclear factor 4

Sexual attraction and perception, governed by separate genetic circuits in different organs, are crucial for mating and reproductive success, yet the mechanisms of how these two aspects are integrated remain unclear. In Drosophila , the male-specific isoform of Fruitless (Fru), Fru M , is known as a master neuro-regulator of innate courtship behavior to control perception of sex pheromones in sensory neurons. Here we show that the non-sex specific Fru isoform (Fru COM ) is necessary for pheromone biosynthesis in hepatocyte-like oenocytes for sexual attraction. Loss of Fru COM in oenocytes resulted in adults with reduced levels of the cuticular hydrocarbons (CHCs), including sex pheromones, and show altered sexual attraction and reduced cuticular hydrophobicity. We further identify Hepatocyte nuclear factor 4 ( Hnf4 ) as a key target of Fru COM in directing fatty acid conversion to hydrocarbons in adult oenocytes. fru - and Hnf4 -depletion disrupts lipid homeostasis, resulting in a novel sex-dimorphic CHC profile, which differs from doublesex - and transformer -dependent sexual dimorphism of the CHC profile. Thus, Fru couples pheromone perception and production in separate organs for precise coordination of chemosensory communication that ensures efficient mating behavior. Teaser Fruitless and lipid metabolism regulator HNF4 integrate pheromone biosynthesis and perception to ensure robust courtship behavior.