Slit regulates subcellular-specific targeting of dendrites and axons in the Drosophila brain

Abstract

Proper nervous system functioning requires axons or dendrites targeting to specific subcellular domains of target neurons to form precise connections. Using mushroom body output neurons (MBONs) and dopaminergic neurons (DAN) in the Drosophila mushroom body as a model, we demonstrate that subcellular-specific targeting of MBON dendrites and DAN axons is regulated by repulsion between their dendrites/axons in neighboring subcellular domains. We further show that Slit mediates such repulsion by binding to distinct Robo receptors in different neurons. Loss of Slit-mediated repulsion leads to expansion of MBON dendrites and DAN axons into neighboring compartments, formation of ectopic synapses, and altered learning and memory. Our findings reveal a critical role of Slit-mediated repulsion between neighboring compartments in regulating subcellular-specific dendrite and axon targeting.