Repulsions instruct synaptic partner matching in an olfactory circuit - Nature

"A fundamental question in neural development is how the vast number of neurons precisely select their synaptic partners to form functional circuits. Neural circuit wiring involves multiple coordinated developmental steps: axon guidance to target regions, dendrite patterning and synaptic partner matching followed by synaptogenesis5,6,7. Even though axon guidance and dendrite patterning can greatly reduce the number of potential partners a neuron encounters at a given time and region8, a developing axon must select specific partners among multiple nearby non-partners1,2."

"It is well established that axon guidance involves both attraction towards the target region and repulsion away from non-target regions9,10. Repulsion mediated by CSPs is also used in establishing topographic maps11, subregion target selection12, and dendritic and axonal self-avoidance2. However, most known CSPs that instruct the final steps of synaptic partner selection act through attraction. These include homophilic attraction of teneurins (Ten-m and Ten-a) in Drosophila olfactory and neuromuscular systems13,14, heterophilic attractions among members of the immunoglobulin superfamily of CSPs in multiple Drosophila circuits15,16,17,18,19,20,21,22, and homophilic attraction mediated by immunoglobulin23 or cadherin24,25 families of CSPs in the vertebrate retina."

Neural circuit wiring requires coordinated developmental steps: axon guidance to target regions, dendrite patterning, synaptic partner matching, and synaptogenesis. Axon guidance and dendrite patterning reduce potential partners but developing axons still must choose specific partners among nearby non-partners. Axon guidance uses both attraction toward target regions and repulsion from non-target regions. Repulsion mediated by cell-surface proteins (CSPs) contributes to topographic map formation, subregion target selection, and dendritic and axonal self-avoidance. Most known CSPs that instruct final synaptic partner choice act through attraction, exemplified by teneurins, immunoglobulin superfamily members, and cadherins, while few repulsive examples have been described.

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