Wnt signalling and aggression in Drosophila melanogaster from neurogenetics to candidate-drugtargets.

Aggressive behavior ensures survival and reproduction. During encounters with conspecific rivals when competing for food, territory or mating partners, the correct integration of sensory cues is required to allow an animal to adapt its behavior according to the situation presented. Integration of environmental cues depends on accurate detection of sensory stimuli, their transduction to higher order brain regions and the ability to translate this information into an appropriate behavioral response. Currently, the role of various sensory modalities in aggression has not been studied in detail.

We investigated the role of the auditory system and the Wg signaling pathway in the olfactory circuit based on previous genetic correlations of these sensory systems and signaling pathway with Drosophila aggression. As sensory communication is a component of aggressive behavior in various species, we hypothesized that:

Hearing is an important sensory modality in Drosophila aggressive behavior

In Drosophila, wing threats generate specific sound patterns during male-male agonistic interactions. It remained an open question whether these aggression songs function as acoustic signals in terms of modulating an opponent’s behavior during aggressive interactions. We therefore analyzed in a systematic way whether aggression songs generated by male flies affect agonistic behavior. We show that impairing the mechanics of the fly’s antennal sound receiver reduces male-male aggression. Silencing the AB sound‑sensitive neurons in the Johnston’s organ (JO) or interfering with signal transduction genes in these neurons also reduces aggressive encounters, indicating that acoustic signals influence behavior. This is highlighted by the observation that agonistic sounds increase aggression, whereas courtship songs reduce aggression. These results suggest that male-derived acoustic signals are perceived and interpreted by male Drosophila melanogaster in order to promote context-appropriate behavior.

Wnt signaling acts at the level of the olfactory-mushroom body circuit to control aggression

The mechanisms active in the olfactory circuit regulating Drosophila aggression are unknown. We showed that Wg signaling plays a role in olfaction-regulated aggression. The loss of wingless (wg) and frizzled 2 (fz2) in the olfactory‑mushroom body neuronal circuit renders male flies less aggressive and hints to a role for Wnt signaling in the transduction of olfactory or pheromonal aggression-evoking stimuli to the mushroom bodies (MBs). Consistent with these results, we found that presenting flies with different concentrations of the male pheromone 11‑cis‑vaccenyl acetate (cVA) under wg and fz2 knockdown conditions in the adult olfactory system results in the loss of a cVA-induced behavioral response. Furthermore, we show that loss of Wg signaling in the antennal lobe (AL) and MBs affects postsynaptic Kenyon cell (KC) bouton microglomeruli size and Ca2+ responses. These results indicate that olfaction-induced aggression responses depend on Wg signaling-regulated transmission of olfactory stimuli and synaptic plasticity.

Taken together we have defined the relative importance of the auditory system by examining the role of JO and sound input in aggressive behavior and show that male fruitflies can detect and interpret intraspecific acoustic signals and adapt their behavioral response to the context reflected by these acoustic signals. In another study we investigated the spatiotemporal role of Wnt signaling in the olfactory neuronal circuit and found that olfaction-induced aggression responses are regulated by Wg signaling. In summary, we conclude that auditory and olfactory information are prominent modulatory factors of Drosophila male aggressive behavior.