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Dual origins of the mammalian accessory olfactory bulb revealed by an evolutionarily conserved migratory stream

Nature Neuroscience volume 16, pages 157–165 (2013)Cite this article

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Abstract

The accessory olfactory bulb (AOB) is a critical olfactory structure that has been implicated in mediating social behavior. It receives input from the vomeronasal organ and projects to targets in the amygdaloid complex. Its anterior and posterior components (aAOB and pAOB) display molecular, connectional and functional segregation in processing reproductive and defensive and aggressive behaviors, respectively. We observed a dichotomy in the development of the projection neurons of the aAOB and pAOB in mice. We found that they had distinct sites of origin and that different regulatory molecules were required for their specification and migration. aAOB neurons arose locally in the rostral telencephalon, similar to main olfactory bulb neurons. In contrast, pAOB neurons arose caudally, from the neuroepithelium of the diencephalic-telencephalic boundary, from which they migrated rostrally to reach their destination. This unusual origin and migration is conserved in Xenopus, providing an insight into the origin of a key component of this system in evolution.

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Figure 1: pAOB projection neurons migrate from the caudal telencephalon.
Figure 2: The DTB is the origin of the pAOB stream.
Figure 3: In utero electroporation reveals a stream of cells migrating from the caudal telencephalon to the pAOB.
Figure 4: Distinct mechanisms of pAOB and aAOB specification and migration.
Figure 5: pAOB cells do not use mechanisms required by Cajal-Retzius cells or the LOT tract.
Figure 6: Shh can guide the pAOB stream trajectory.
Figure 7: AOB markers in Xenopus suggest a migrating stream from the DTB.
Figure 8: Fluorescent microsphere injection reveals a DTB-to-AOB migration in Xenopus.

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Acknowledgements

We thank A. Faedo (University of California, San Francisco), E.A. Grove (University of Chicago), R. Kageyama (Kyoto University), F.D. Porter (US National Institute of Child Health and Human Development), S. Retaux (Centre national de la recherche scientifique, France), T. Sargent (US National Institute of Child Health and Human Development), N. Tamamaki (Kumamoto University) and T. Williams (University of Colorado, Denver) for gifts of plasmid DNA, and the Tata Institute of Fundamental Research Animal House staff for excellent support. We thank M. Hynes (Stanford University) for Netrin1 mutants and L. Richards (Queensland Brain Institute) for Slit1; Slit2 double mutants. This work was supported by a Swarnajayanti Fellowship (Department of Science and Technology, India), a grant from the Department of Biotechnology and a grant from the Lady Tata Memorial Trust to S.T., and a Kanwal Rekhi Career Development Award (Tata Institute of Fundamental Research Endowment Fund) to B.S.

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Authors and Affiliations

  1. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India

    Dhananjay Huilgol, Bhaskar Saha, Achira Roy & Shubha Tole

  2. Department of Physiology and Biophysics, State University of New York, Buffalo, New York, USA

    Susan Udin

  3. Brain Science Institute, RIKEN, Wako, Japan

    Tomomi Shimogori

  4. Center for Developmental Biology, RIKEN, Kobe, Japan

    Shinichi Aizawa

  5. Department of Pathology, University of Washington, Seattle, Washington, USA

    Robert F Hevner

  6. University La Laguna, Tenerife, Spain

    Gundela Meyer

  7. Center for Advanced Biomedical Science, Waseda University, Tokyo, Japan

    Toshio Ohshima

  8. Department of Neurology, University of California, San Francisco, California, USA

    Samuel J Pleasure

  9. US National Institutes of Health,, Bethesda, Maryland, USA

    Yangu Zhao

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Contributions

D.H. and S.T. planned the experiments and wrote the paper. D.H., B.S. and S.T. analyzed the data. D.H. performed experiments for all figures. S.U. performed the fluorescent microsphere placements shown in Figure 8 and provided the tadpoles. T.S. performed the in utero electroporation experiments shown in Figure 3 and Supplementary Figure 2. B.S. contributed to Figures 1 and 2. A.R. contributed to Figure 2 and Supplementary Figure 1. Mutant embryos were contributed by S.A. (Emx1; Emx2 double mutant), R.F.H. (Tbr1), G.M. (P73), T.O. (Cdk5), S.J.P. (Cxcr4) and Y.Z. (Lhx5).

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Correspondence to Shubha Tole.

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Huilgol, D., Udin, S., Shimogori, T. et al. Dual origins of the mammalian accessory olfactory bulb revealed by an evolutionarily conserved migratory stream. Nat Neurosci 16, 157–165 (2013). https://doi.org/10.1038/nn.3297

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