Integrating lipid metabolism, pheromone production and perception by Fruitless and Hepatocyte Nuclear Factor 4.

Abstract

Sexual attraction and perception are crucial for mating and reproductive success. In <i>Drosophila melanogaster</i>, the male-specific isoform of Fruitless (Fru), Fru^M, is a known master neuro-regulator of innate courtship behavior to control the 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 cuticular hydrocarbons (CHCs), including sex pheromones, and show altered sexual attraction and reduced cuticular hydrophobicity. We further identify <i>Hepatocyte nuclear factor 4</i> (<i>Hnf4</i>) as a key target of Fru^COM in directing fatty acid conversion to hydrocarbons. <i>Fru</i> or <i>Hnf4</i> depletion in oenocytes disrupts lipid homeostasis, resulting in a sex-dimorphic CHC profile that differs from <i>doublesex-</i> and <i>transformer-</i>dependent CHC dimorphism. Thus, Fru couples pheromone perception and production in separate organs to regulate chemosensory communications and ensure efficient mating behavior.