Transneuronal interactions facilitate axonal compartment formation

Precise connectivity of neurites to subcellular domains is a conserved feature of complex circuits, but the mechanisms defining precise wiring are largely unknown. The Drosophila mushroom-body is uniquely poised to study subcellular wiring as the adult γ-lobe harbors five distinct compartments, defined by localized innervations of other neuronal populations. Here we identify mechanisms required for precise wiring of γ-axons: Dpr12 and its interacting protein DIP-δ are both enriched at the γ4/5 compartments. However, while Dpr12 is cell-autonomously required in γ-neurons, DIP-δ acts in dopaminergic neurons for the formation of the γ4/5 compartments and the correct network architecture. Furthermore, γ-axons grow into regions preoccupied by DIP-δ+ neurons suggesting that they innervate a prepatterned lobe. Thus, transneuronal interactions that mediate precise wiring are required for axon compartmentalization.