Epistasis and pleiotropy feature prominently in the genetic architecture of quantitative traits but are difficult to assess in outbred populations. We performed a diallel cross among coisogenic Drosophila P-element mutations associated with hyperaggressive behavior and showed extensive epistatic and pleiotropic effects on aggression, brain morphology, and genome-wide transcript abundance in head tissues. Epistatic interactions were often of greater magnitude than homozygous effects, and the topology of epistatic networks varied among these phenotypes. The transcriptional signatures of homozygous and double heterozygous genotypes derived from the six mutations imply a large mutational target for aggressive behavior and point to evolutionarily conserved genetic mechanisms and neural signaling pathways affecting this universal fitness trait.

Aggressive behavior is widely present throughout the animal kingdom and is crucial to ensure survival and reproduction. Aggressive actions serve to acquire territory, food, or mates and in defense against predators or rivals; while in some species these behaviors are involved in establishing a social hierarchy. Aggression is a complex behavior, influenced by a broad range of genetic and environmental factors. Recent studies in Drosophila provide insight into the genetic basis and control of aggression. The state of the art on aggression in Drosophila and the many opportunities provided by this model organism to unravel the genetic and neurobiological basis of aggression are reviewed.

Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.A ggression is one of the most important social behaviors in nature, ensuring reproduction and survival when competing for food, territory, or mating partners (1). Aggression is a complex behavior shaped by many factors, including a complex genetic architecture, the integration of various neurotransmitter and hormone systems, and a range of environmental factors (2).Correct integration and processing of sensory information are crucial to evoke an appropriate behavioral response. Previous studies have implicated different sensory modalities in the regulation of aggressive behavior in Drosophila melanogaster, including the olfactory, gustatory, and visual systems (3-6).Another important sensory modality in Drosophila is hearing. Stereotypic sound patterns generated by wing vibration and their behavioral significance have been extensively studied in the context of Drosophila courtship (7-12). On the contrary, nothing is known about the impact of hearing on aggressive behavior. Furthermore, although agonistic sound pulses are known to be generated during aggressive encounters, it is unknown whether they serve as acoustic communication signals to modulate behavior (13).The Drosophila auditory organ, Johnston's organ (JO), is situated in the fly's antenna (Fig. 1A) (14-17). Antennal displacement leads to activation of ∼500 chordotonal stretch-receptor neurons in the JO, which contains AB neurons responsive to sound-evoked vibrations and CE neurons sensitive to sustained antennal deflections caused by gravity and wind (Fig. 1A) (18). The sensory neuron subclasses each innervates a particular region of the antennal mechanosensory and motor center (AMMC), the primary processing center for auditory input in the fly brain (18).In this study, we use mechanical disruption and genetic approaches in D. melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We show that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ induce abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data provide evidence on the r...