Slit regulates compartment-specific targeting of dendrites and axons in the brain.

Proper functioning of the nervous system requires precise neuronal connections at subcellular domains, which can be achieved by projection of axons or dendrites to subcellular domains of target neurons. Here we studied subcellular-specific targeting of dendrites and axons in the mushroom body (MB), where mushroom body output neurons (MBONs) and local dopaminergic neurons (DAN) project their dendrites and axons, respectively, to specific compartments of MB axons. Through genetic ablation, we demonstrate that compartment-specific targeting of MBON dendrites and DAN axons involves mutual repulsion of MBON dendrites and/or DAN axons between neighboring compartments. We further show that Slit expressed in subset of DANs mediates such repulsion by acting through different Robo receptors in different neurons. Loss of Slit-mediated repulsion leads to projection of MBON dendrites and DAN axons into neighboring compartments, resulting formation of ectopic synaptic contacts between MBONs and DANs and changes in olfactory-associative learning. Together, our findings suggest that Slit-mediated repulsion controls compartment-specific targeting of MBON dendrites and DAN axons, which ensures precise connections between MBON dendrites and DAN axons and proper learning and memory formation.