Teneurins Instruct Synaptic Partner Matching in an Olfactory Map

Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and post-synaptic partners are matched. To ensure the proper relay of olfactory information in flies, axons of ~50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of ~50 classes of projection neurons (PNs). Using genetic screens, we identified two evolutionarily conserved EGF-repeat transmembrane Teneurins, Ten-m and Ten-a, as synaptic partner matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.