The Vap33/Eph/Vav/Cdc42 complex confers temporal specification to the outgrowth of primary dendrites in Drosophila neurons

SUMMARYThe formation of primary dendrites (dendritogenesis) significantly affects the overall orientation and coverage of dendritic arborization, limiting the number and types of inputs a neuron can receive. Previously we reported how a Drosophila motoneuron spatially controls the positioning of dendritogenesis through the Dscam1/Dock/Pak1 pathway; however, how the neuron defines the timing of this process remains elusive. Here we show that the Eph receptor tyrosine kinase provides a temporal cue. We find that, at the onset of dendritogenesis, the Eph receptor recruits the Rho Family GEF Vav to the intracellular domain of Eph, which transiently activates the Cdc42 family of small GTPase. We also show that vap33 (vesicle-associated membrane protein-associated protein) mutants exhibit defects in Cdc42 activation and dendritic outgrowth, indicating Vap33 may play an upstream role in Eph signaling. Together, our result and previous studies argue that the formation of primary dendrites requires the proximity of active Cdc42 and membrane-anchored Pak1 driven by collaborative action between two distinct signaling complexes, Vap33/Eph/Vav and Dscam1/Dock. Signal integration from multiple input pathways would represent a general mechanism for the spatiotemporal precision of dendrite branch formation.