Ephrin-mediated dendrite-dendrite repulsion regulates compartment-specific targeting of dendrites in the central nervous system

Neurons often forms synaptic contacts at specific subcellular domains to differentially regulate the activity of target neurons. However, how dendrites are targeted to specific subcellular domains of axons is rarely studied. Here we use Drosophila mushroom body out neurons (MBONs) and local dopaminergic neurons (DANs) as a model system to study how dendrites and axons are targeted to specific subcellular domains (compartments) of mushroom body axonal lobes to form synaptic contacts. We found that Ephrin-mediated dendrite-dendrite repulsion between neighboring compartments restricts the projection of MBON dendrites to their specific compartments and prevents the formation of ectopic synaptic connections with DAN axons in neighboring compartments. Meanwhile, DAN neurons in a subset of compartments may also depend on their partner MBONs for projecting their axons to a specific compartment and cover the same territory as their partner MBON dendrites. Our work reveals that compartment-specific targeting of MBON dendrites and DAN axons is regulated in part by a combination of dendrite-dendrite repulsion between neighboring compartments and dendrite-axon interactions within the same compartment.