A Drosophila proto-oncogene homolog controls aggression via aminergic neurons

Modulation of action choices according to the environmental context is crucial for animal survival and reproductive success1. Aggression, despite its general importance as a social behavior2, can become detrimental if uncontrolled3,4. However, the genetic and neural basis for aggression control through active suppression remains largely unknown. Here we found nvy, a Drosophila homolog of vertebrate myeloid translocation gene (MTG)5 involved in transcriptional regulation6-8, suppresses aggression through a specific subset of neurons. Mutation of the nvy gene resulted in hyper-aggressiveness, which was rescued by neuronal expression of human MTGs as well as Drosophila nvy. The mutant exhibited persistent aggression under various contexts in which wild-type flies switch their behavioral patterns. Knockdown of nvy in octopaminergic/tyraminergic (OA/TA) neurons increased aggression, phenocopying the nvy deletion. Cell-type specific transcriptomics on OA/TA neurons derived from the nvy mutants revealed aggression-controlling genes that are likely downstream of nvy. Moreover, we found that the nvy-expressing OA/TA neuronal subpopulations specifically suppress aggression. Our results presents a powerful genetic model to unravel not only the neuronal systems that modulate aggression in a social context-dependent manner, but also the conserved molecular mechanism underlying the tumorigenesis caused by the MTG mutations. Transcriptional profiles of octopaminergic/tyraminergic neurons of wild-type and nervy-mutant fruit flies using single-cell RNA-sequencing technology.