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Leucine-rich repeat transmembrane proteins instruct discrete dendrite targeting in an olfactory map

Abstract

Olfactory systems utilize discrete neural pathways to process and integrate odorant information. In Drosophila, axons of first-order olfactory receptor neurons (ORNs) and dendrites of second-order projection neurons (PNs) form class-specific synaptic connections at 50 glomeruli. The mechanisms underlying PN dendrite targeting to distinct glomeruli in a three-dimensional discrete neural map are unclear. We found that the leucine-rich repeat (LRR) transmembrane protein Capricious (Caps) was differentially expressed in different classes of PNs. Loss-of-function and gain-of-function studies indicated that Caps instructs the segregation of Caps-positive and Caps-negative PN dendrites to discrete glomerular targets. Moreover, Caps-mediated PN dendrite targeting was independent of presynaptic ORNs and did not involve homophilic interactions. The closely related protein Tartan was partially redundant with Caps. These LRR proteins are probably part of a combinatorial cell-surface code that instructs discrete olfactory map formation.

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Figure 1: Caps is differentially expressed in the developing antennal lobe.
Figure 2: Dendrite targeting phenotypes of caps−/− neuroblast clones.
Figure 3: Cell-autonomous requirement of Caps in Caps-positive PNs for dendrite targeting.
Figure 4: Dendrite targeting phenotypes of Caps misexpression in Caps-negative PNs.
Figure 5: caps is not required in ORNs for their axon targeting.
Figure 6: Caps-mediated PN dendrite targeting is independent of ORNs.
Figure 7: Caps does not mediate homophilic interactions for PN dendrite targeting.
Figure 8: trn enhances caps phenotypes in PN dendrite targeting.

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Acknowledgements

We thank A. Nose (University of Tokyo), S. Cohen (Temasek Life Sciences Laboratory), M. Freeman (Medical Research Council Laboratory of Molecular Biology), S. Hayashi (RIKEN Center for Developmental Biology) and M. Milan (Icrea and Parc Cientific de Barcelona) for fly stocks and reagents; the Bloomington, Szeged, Kyoto and Harvard Stock Centers for fly stocks; M. Spletter for making antennal lobe schemes; and T. Clandinin, K. Miyamichi, M. Spletter, L. Sweeney, J. Wu, X. Yu, D. Berdink and other laboratory members for comments and discussions. This work was supported by US National Institutes of Health grant R01-DC005982. L.L. is an investigator of the Howard Hughes Medical Institute.

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W.H. performed most of the experiments and analyzed the data. H.Z. initiated the overexpression screen. C.J.P. provided the GH146-Flp transgenic fly line. G.B. assisted in some experiments. M.K. and K.Z. provided the database and collection of fly strains for the overexpression screen. W.H. and L.L. designed the experiments and wrote the paper.

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Correspondence to Liqun Luo.

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Hong, W., Zhu, H., Potter, C. et al. Leucine-rich repeat transmembrane proteins instruct discrete dendrite targeting in an olfactory map. Nat Neurosci 12, 1542–1550 (2009). https://doi.org/10.1038/nn.2442

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