Tailless and Atrophin control Drosophila aggression by regulating neuropeptide signalling in the pars intercerebralis

Aggressive behaviour is widespread throughout the animal kingdom. However, its mechanisms are poorly understood, and the degree of molecular conservation between distantly related species is unknown. Here we show that knockdown of tailless (tll) increases aggression in Drosophila, similar to the effect of its mouse orthologue Nr2e1. Tll localizes to the adult pars intercerebralis (PI), which shows similarity to the mammalian hypothalamus. Knockdown of tll in the PI is sufficient to increase aggression and is rescued by co-expressing human NR2E1. Knockdown of Atrophin, a Tll co-repressor, also increases aggression, and both proteins physically interact in the PI. tll knockdown-induced aggression is fully suppressed by blocking neuropeptide processing or release from the PI. In addition, genetically activating PI neurons increases aggression, mimicking the aggression-inducing effect of hypothalamic stimulation. Together, our results suggest that a transcriptional control module regulates neuropeptide signalling from the neurosecretory cells of the brain to control aggressive behaviour.