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Molecular organization of vomeronasal chemoreception

Abstract

The vomeronasal organ (VNO) has a key role in mediating the social and defensive responses of many terrestrial vertebrates to species- and sex-specific chemosignals1. More than 250 putative pheromone receptors have been identified in the mouse VNO2,3, but the nature of the signals detected by individual VNO receptors has not yet been elucidated. To gain insight into the molecular logic of VNO detection leading to mating, aggression or defensive responses, we sought to uncover the response profiles of individual vomeronasal receptors to a wide range of animal cues. Here we describe the repertoire of behaviourally and physiologically relevant stimuli detected by a large number of individual vomeronasal receptors in mice, and define a global map of vomeronasal signal detection. We demonstrate that the two classes (V1R and V2R) of vomeronasal receptors use fundamentally different strategies to encode chemosensory information, and that distinct receptor subfamilies have evolved towards the specific recognition of certain animal groups or chemical structures. The association of large subsets of vomeronasal receptors with cognate, ethologically and physiologically relevant stimuli establishes the molecular foundation of vomeronasal information coding, and opens new avenues for further investigating the neural mechanisms underlying behaviour specificity.

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Figure 1: Egr1 expression is robustly induced by pheromone-evoked VNO neuronal activation.
Figure 2: Widespread activation of VNO receptors by conspecific and heterospecific cues.
Figure 3: Receptor responses to sex-specific cues.
Figure 4: Receptor responses to heterospecific cues.
Figure 5: Sulphated steroids detection by V1Rs.

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Acknowledgements

We acknowledge H. Fisher, H. Hoekstra, E. Kay, M. Kirchgessner, N. Uchida, A. Wang, X.-D. Wang, B. Watson, W. Tong, Harvard Museum of Natural History, Harvard Concord Field Station, Museum of Science, Boston, and New England Wildlife Center, for providing stimulus materials used in this study, L. Looger for the G-CaMP3 construct, M. Wienisch, F. Markopoulos and D. Mak for help with electrophysiology and imaging experiments, and B. Goetze and the Harvard Center for Biological Imaging for help with microscopy. We also thank members of the Dulac laboratory for critical reading of the manuscript, S. Andreeva for technical support and R. Hellmiss for help with figure artwork. This work was supported by the NIDCD at the National Institute of Health, the Howard Hughes Medical Institute and the Damon Runyon Cancer Research Foundation (Y.I., DRG-1981-08).

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Y.I. and C.D. designed the study. Y.I., S.S. and T.T. designed and generated RNA probes, performed RNA in situ hybridization, and analysed data. L.P.-L. performed pilot experiments for data shown in Fig. 1 and produced recombinant ESP1. Y.I. and V.K. performed calcium imaging and electrophysiology. V.N.M. supervised physiology experiments. Y.I. and C.D. wrote the paper.

Corresponding author

Correspondence to Catherine Dulac.

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The authors declare no competing financial interests.

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The file contains Supplementary Figures 1-12 with legends and Supplementary Tables 1-2. (PDF 24866 kb)

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Isogai, Y., Si, S., Pont-Lezica, L. et al. Molecular organization of vomeronasal chemoreception. Nature 478, 241–245 (2011). https://doi.org/10.1038/nature10437

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