Repulsive interactions instruct synaptic partner matching in an olfactory circuit

TL;DR

The study shows repulsive interactions between proteins help neurons avoid incorrect connections in the fruit fly's smell circuit.

Contribution

The paper identifies three new repulsive cell-surface protein pairs that prevent incorrect synaptic connections in Drosophila olfactory circuits.

Findings

Three CSP pairs (Toll2–Ptp10D, Fili–Kek1, Hbs/Sns–Kirre) mediate repulsive interactions in the olfactory circuit.

Loss or overexpression of these proteins causes synaptic partner matching deficits.

These CSP pairs are differentially expressed in other brain regions, suggesting broader roles.

Abstract

Neurons exhibit extraordinary precision in selecting synaptic partners. Whereas cell-surface proteins (CSPs) mediating attractive interactions between developing axons and dendrites have been shown to instruct synaptic partner matching1,2, it is less clear the degree to which repulsive interactions play a role. Here, using a genetic screen guided by single cell transcriptomes3,4, we identified three CSP pairs—Toll2–Ptp10D, Fili–Kek1, and Hbs/Sns–Kirre—in mediating repulsive interactions between non-partner olfactory receptor neuron (ORN) axons and projection neuron (PN) dendrites in the developing Drosophila olfactory circuit. Each CSP pair exhibits inverse expression patterns in the select PN-ORN partners. Loss of each CSP in ORNs led to similar synaptic partner matching deficits as the loss of its partner CSP in PNs, and mistargeting phenotypes caused by overexpressing one CSP could be suppressed by loss of its partner CSP. Each CSP pair is also differentially expressed in other brain regions. Together, our data reveal that multiple repulsive CSP pairs work together to ensure precise synaptic partner matching during development by preventing neurons from forming connections with non-cognate partners.

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