Transneuronal Dpr12/DIP-δ interactions facilitate compartmentalized dopaminergic innervation of Drosophila mushroom body axons

The mechanisms controlling wiring of neuronal networks are largely unknown. The stereotypic architecture of the Drosophila mushroom-body (MB) offers a unique system to study circuit assembly. The adult medial MB {gamma}-lobe is comprised of a long bundle of axons that wires with specific modulatory and output neurons in a tiled manner defining five distinct zones. We found that the immunoglobulin superfamily protein Dpr12 is cell-autonomously required in {gamma}-neurons for their developmental regrowth into the distal {gamma}4/5 zones, where both Dpr12 and its interacting protein, DIP-{delta}, are enriched. DIP-{delta} functions in a subset of dopaminergic neurons that wire with {gamma}-neurons within the {gamma}4/5 zone. During metamorphosis, these dopaminergic projections arrive to the {gamma}4/5 zone prior to {gamma}-axons, suggesting that {gamma}-axons extend through a prepatterned region. Thus, Dpr12/DIP-{delta} transneuronal interaction is required for {gamma}4/5 zone formation. Our study sheds light onto molecular and cellular mechanisms underlying circuit formation within subcellular resolution.