Natural aggressiveness is commonly observed in all animal species, and is displayed frequently when animals compete for food, territory and mating. Aggression is an innate behaviour, and is influenced by both environmental and genetic factors. However, the genetics of aggression remains largely unclear. In this study, we identify the peacefulness (pfs) gene as a novel player in the control of male-male aggression in Drosophila. Mutations in pfs decreased intermale aggressiveness, but did not affect locomotor activity, olfactory avoidance response and sexual behaviours. pfs encodes for the evolutionarily conserved molybdenum cofactor (MoCo) synthesis 1 protein (Mocs1), which catalyzes the first step in the MoCo biosynthesis pathway. Neuronal-specific knockdown of pfs decreased aggressiveness. By contrast, overexpression of pfs greatly increased aggressiveness. Knocking down Cinnamon (Cin) catalyzing the final step in the MoCo synthesis pathway, caused a pfs-like aggression phenotype. In humans, inhibition of MoCo-dependent enzymes displays anti-aggressive effects. Thus, the control of aggression by Pfs-dependent MoCo pathways may be conserved throughout evolution.Electronic supplementary materialThe online version of this article (10.1186/s13041-018-0417-0) contains supplementary material, which is available to authorized users.

Restriction of adjacent same-type axons/dendrites to separate single columns for specific neuronal connections is commonly observed in vertebrates and invertebrates, and is necessary for proper processing of sensory information. Columnar restriction is conceptually similar to tiling, a phenomenon referring to the avoidance of neurites from adjacent same-type neurons. The molecular mechanism underlying the establishment of columnar restriction or axonal/dendritic tiling remains largely undefined. Here, we identify Turtle (Tutl), a member of the conserved Tutl/Dasm1/IgSF9 subfamily of the Ig superfamily, as a key player in regulating the tiling pattern of R7 photoreceptor terminals in Drosophila. Tutl functions to prevent fusion between two adjacent R7 terminals, and acts in parallel to the Activin pathway. Tutl mediates homophilic cell-cell interactions. We propose that extrinsic terminal-terminal recognition mediated by Tutl, acts in concert with intrinsic Activin-dependent control of terminal growth, to restrict the connection made by each R7 axon to a single column.

Proper recognition between axons and glial processes is required for the establishment of axon ensheathment in the developing nervous system. Recent studies have begun to reveal molecular events underlying developmental control of axon-glia recognition. In our previous work, we showed that the transmembrane protein Borderless (Bdl) is specifically expressed in wrapping glia (WG), and is required for the extension of glial processes and the ensheathment of photoreceptor axons in the developing Drosophila visual system. The exact mechanism by which Bdl mediates axon-glia recognition, however, remains unknown. Here, we present evidence showing that Bdl interacts with the Ig transmembrane protein Turtle (Tutl). Tutl is specifically expressed in photoreceptor axons. Loss of tutl in photoreceptors, like loss of bdl in WG, disrupts glial extension and axon ensheatment. Epistasis analysis shows that Tutl interacts genetically with Bdl. Tutl interacts with Bdl in trans in cultured cells. We propose that Tutl interacts with Bdl in mediating axon-glia recognition for WG extension and axon ensheathment.

Establishment of synaptic connections in the neuropils of the developing nervous system requires the coordination of specific neuriteneurite interactions (i.e., axon-axon, dendrite-dendrite and axon-dendrite interactions). The molecular mechanisms underlying coordination of neurite-neurite interactions for circuit assembly are incompletely understood. In this report, we identify a novel Ig superfamily transmembrane protein that we named Borderless (Bdl), as a novel regulator of neurite-neurite interactions in Drosophila. Bdl induces homotypic cell-cell adhesion in vitro and mediates neurite-neurite interactions in the developing visual system. Bdl interacts physically and genetically with the Ig transmembrane protein Turtle, a key regulator of axonal tiling. Our results also show that the receptor tyrosine phosphatase leukocyte common antigen-related protein (LAR) negatively regulates Bdl to control synaptic-layer selection. We propose that precise regulation of Bdl action coordinates neurite-neurite interactions for circuit formation in Drosophila.

Semaphorin family proteins are well-known axon guidance ligands. Recent studies indicate that certain transmembrane Semaphorins can also function as guidance receptors to mediate axon-axon attraction or repulsion. The mechanisms by which Semaphorin reverse signaling modulates axon-surface affinity, however, remain unknown. In this study, we reveal a novel mechanism underlying upregulation of axon-axon attraction by Semaphorin-1a (Sema1a) reverse signaling in the developing Drosophila visual system. Sema1a promotes the phosphorylation and activation of Moesin (Moe), a member of the ezrin/radixin/moesin family of proteins, and downregulates the level of active Rho1 in photoreceptor axons. We propose that Sema1a reverse signaling activates Moe, which in turn upregulates Fas2-mediated axon-axon attraction by inhibiting Rho1.T he Semaphorin family of proteins are well-known axon guidance cues or ligands, which activate their receptors on a variety of axons to control axonal pathfinding, fasciculation, branching, and target selection in vertebrates and invertebrates (1, 2). Recent studies demonstrate that certain transmembrane Semaphorins can also function as a receptor to mediate downstream signaling events in both vertebrates and invertebrates (3-7). For example, we show that the transmembrane Semaphorin1a (Sema1a) functions as an axon guidance receptor for PlexinA (PlexA) in mediating reverse signaling in the developing Drosophila visual system (3, 8). Sema1a reverse signaling promotes photoreceptor (R cell) axon-axon attractions during the establishment of R-cell-to-optic-lobe connections (8). A recent study by Kolodkin and colleagues also demonstrates that Sema1a reverse signaling mediates axon-axon repulsion in Drosophila motor axon guidance (6).To understand the mechanisms underlying upregulation of axon-axon attractions by Sema1a reverse signaling, we set out to examine potential genetic interactions between Sema1a and other genes in R-cell axon guidance. The establishment of R-cell-to-optic-lobe connections in the Drosophila adult visual system begins at the third-instar larval stage (9). At the thirdinstar larval stage, differentiating R cells in the eye-imaginal disk extend axons through the optic stalk into the developing optic lobe. R1-R6 axons terminate at the superficial lamina layer, where their growth cones closely associate with each other at the lamina termination site. R7 and R8 axons bypass the lamina and terminate in the deeper medulla layer.In this study, we present evidence that Sema1a reverse signaling promotes R-cell axon-axon attraction by upregulating the adhesive function of Fasciclin 2 (Fas2). Sema1a interacts genetically and physically with Moesin (Moe), a member of the ezrin/radixin/moesin (ERM) family proteins, and downregulates the level of active Rho1. Our results support that Sema1a-induced reduction in the level of active Rho1 in R-cell axons contributes to an increase in Fas2-mediated R-cell axon-axon attraction. Results Sema1aInteracts with Fas2 in Regulating R-Cell Axonal Projec...