Histamine signalingviathe metabotropic receptorTrapped in endoderm 1regulates courtship initiation inDrosophila melanogaster

Understanding the role of genes in directing behavior is one of the primary goals of neuroscience. Mating behavior in Drosophila is controlled by male-specific splicing of the master regulatory gene fruitless ( fru ), and the male-specific splice form, fru M , is both necessary and sufficient for all aspects of the courtship ritual. We have previously described the role of Trapped in endoderm 1 ( Tre1 ) in courtship behavior. Tre1 encodes an orphan G-protein-coupled receptor that is essential for normal courtship behavior in male flies. We previously found that feminizing Tre1 -expressing cells in males via expression of the female-specific splicing factor Transformer (Tra F ) resulted in rapid courtship initiation. Here we confirm that Tre1 is required in neurons for normal courtship behavior, and present genetic evidence that Tre1 acts through the downregulation of the E-cadherin Shotgun, and that the neurotransmitter histamine is the likely Tre1 ligand. Our findings are the first evidence for metabotropic histamine receptors in Drosophila , and the first to demonstrate a role for histamine in courtship.