Abstract
n vivo axon pathfinding mechanisms in the neuron-dense brain remain relatively poorly characterized.We study theDrosophilamushroom body (MB)axons, whoseaandbbranches connect to differentbrain areas. We show that the Ryk family WNT5receptor, DRL (derailed), which is expressed in thedorsomedial lineages, brain structure precursorsadjacent to the MBs, is required for MBabranchaxon guidance. DRL acts to capture and presentWNT5 to MB axons rather than transduce a WNT5signal. DRL’s ectodomain must be cleaved andshed to guideaaxons. DRL-2, another Ryk, isexpressed within MB axons and functions as a repul-sive WNT5 signaling receptor. Finally, our biochem-ical data support the existence of a ternary complexcomposed of the cleaved DRL ectodomain, WNT5,and DRL-2. Thus, the interaction of MB-extrinsicand -intrinsic Ryks via their common ligand acts toguide MBaaxons