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Teneurins instruct synaptic partner matching in an olfactory map

Abstract

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 postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of 50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of 50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, 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.

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Figure 1: PN–ORN synaptic matching screens identify two Teneurins.
Figure 2: Ten-m and Ten-a are differentially expressed in matching PN and ORN classes.
Figure 3: Loss of Teneurins causes PN–ORN mismatching.
Figure 4: Teneurin overexpression in specific PN classes causes mismatching.
Figure 5: Ten-m promotes homophilic interactions in vitro and in vivo.

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Acknowledgements

We thank V. Favaloro for advice on biochemistry and D. Luginbuhl for technical assistance; K. Zinn for the EP collection; H. Zhu for the initial contribution; R. Wides and S. Baumgartner for teneurin reagents; B. Zhang, Bloomington, Kyoto, Harvard and Vienna Stock Centers for fly stocks; BestGene for injection service; and K. Shen, T. Clandinin, D. Berns, V. Favaloro, X. Gao, S. Hippenmeyer, C. Liu, K. Miyamichi and X. Yu for critiques. Supported by a National Institutes of Health (NIH) grant (R01 DC-005982 to L.L.), and Epilepsy, Neonatology and Developmental Biology Training Grants (NIH 5T32 NS007280 and HD007249 to T.J.M.). L.L. is an investigator of the Howard Hughes Medical Institute.

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W.H. designed and performed all experiments. T.J.M. assisted in some experiments. L.L. supervised the project. W.H. and L.L. wrote the manuscript with feedback from T.J.M.

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Correspondence to Liqun Luo.

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Hong, W., Mosca, T. & Luo, L. Teneurins instruct synaptic partner matching in an olfactory map. Nature 484, 201–207 (2012). https://doi.org/10.1038/nature10926

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