Heterophilic interactions between cell-surface proteins Teneurin-m and Capricious drive dendrite segregation in the Drosophila olfactory circuit.

How dendrites of different neurons segregate into discrete spatial domains during neural circuit assembly is poorly understood. Here, using the Drosophila olfactory system, we found that heterophilic interactions between two cell-surface proteins, Teneurin-m (Ten-m) and Capricious (Caps), drive dendrite segregation. Ten-m and Caps are expressed in largely inverse patterns across projection neuron (PN) types when PNs are establishing their dendritic territories. Loss of Ten-m in Ten-m+ PNs causes their dendrites to invade Caps+ territories, whereas loss of Caps in Caps+ PNs causes dendrite invasion into Ten-m+ territories. Structure-guided mutations that abolish Ten-m-Caps binding disrupt dendrite segregation, whereas the same mutation on Ten-m preserves its homophilic attraction in a synaptic partner matching assay. These results support a model in which mutual repulsions between two inversely expressed cell-surface proteins drive dendrite segregation into discrete glomerular territories.