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

The mechanisms controlling wiring of neuronal networks are not completely understood. The stereotypic architecture of the Drosophila mushroom-body (MB) offers a unique system to study circuit assembly. The adult medial MB ?-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 ?-neurons for their developmental regrowth into the distal ?4/5 zones, where both Dpr12 and its interacting protein, DIP-d, are enriched. DIP-d functions in a subset of dopaminergic neurons that wire with ?-neurons within the ?4/5 zone. During metamorphosis, these dopaminergic projections arrive to the ?4/5 zone prior to ?-axons, suggesting that ?-axons extend through a prepatterned region. Thus, Dpr12/DIP-d transneuronal interaction is required for ?4/5 zone formation. Our study sheds light onto molecular and cellular mechanisms underlying circuit formation within subcellular resolution. Overall design: Transcriptional profiling of drosophila ? neurons perturbed by Hr51 RNAi