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Neuronal fate determinants of adult olfactory bulb neurogenesis

Nature Neuroscience volume 8, pages 865–872 (2005)Cite this article

Abstract

Adult neurogenesis in mammals is restricted to two small regions, including the olfactory bulb, where GABAergic and dopaminergic interneurons are newly generated throughout the entire lifespan. However, the mechanisms directing them towards a specific neuronal phenotype are not yet understood. Here, we demonstrate the dual role of the transcription factor Pax6 in generating neuronal progenitors and also in directing them towards a dopaminergic periglomerular phenotype in adult mice. We present further evidence that dopaminergic periglomerular neurons originate in a distinct niche, the rostral migratory stream, and are fewer derived from precursors in the zone lining the ventricle. This regionalization of the adult precursor cells is further supported by the restricted expression of the transcription factor Olig2, which specifies transit-amplifying precursor fate and opposes the neurogenic role of Pax6. Together, these data explain both extrinsic and intrinsic mechanisms controlling neuronal identity in adult neurogenesis.

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Figure 1: Expression of the transcription factors Pax6 and Olig2 in the SEZ-olfactory bulb pathway.
Figure 2: Functional analysis of the transcription factors Pax6 and Olig2 in adult neurogenesis.
Figure 3: Quantitative localization analysis of infected cells after virus injection into the SEZ or the RMS.
Figure 4: Functional analysis of Pax6 and Olig2 in the specification of neuronal subtypes in adult neurogenesis.

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Acknowledgements

We are particularly grateful to M. Nakafuku for the pMXIG Olig2 and pMXIG Olig2 VP16 constructs; N. Osumi for the pMESPax6engrailed construct; M. Wegner for the antisera directed against Sox10 and P. Durbec for providing PSANCAM antibodies. We also thank A. Bust, M. Öcalan and S. Ankri for excellent technical help. This work was supported by the Deutsche Forschungsgemeinschaft (M.G.) and by the Pasteur Institute (P.M.L., GPH no. 7, 'Stem cells') and the Centre National de la Recherche Scientifique and A.S. was supported by a postdoctoral fellowship from the Pasteur Institute and the Association Française Contre les Myopathies. R.A.-P. is supported by the Israel Science Foundation (401/02) and the German-Israeli Foundation for Scientific Research and Development.

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Author notes

  1. Michael A Hack and Armen Saghatelyan: These authors contributed equally to this work.

Authors and Affiliations

  1. GSF-National Research Center for Environment and Health, Institute for Stem Cell Research, Ingolstädter Landstr. 1, Neuherberg, D-85764, Germany

    Michael A Hack & Magdalena Götz

  2. Laboratory of Perception and Memory, Centre National de la Recherche Scientifique, Unité de Recherche Associée 2182, Pasteur Institute, 25 rue du Dr. Roux, Paris, 75724, Cedex 15, France

    Armen Saghatelyan, Antoine de Chevigny & Pierre-Marie Lledo

  3. Department of Pharmacy, Molecular Pharmacology, Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, Munich, 81377, Germany

    Alexander Pfeifer

  4. Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Ramat Aviv, Tel Aviv, 69987, Israel

    Ruth Ashery-Padan

  5. Institute of Physiology, University of Munich, Pettenkoferstr. 12, Munich, 80336, Germany

    Magdalena Götz

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  1. Michael A Hack
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Correspondence to Pierre-Marie Lledo or Magdalena Götz.

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Supplementary information

Supplementary Fig. 1

Comparison of Pax6 and Olig2 dominant-negative and loss-of-function viral manipulations. (PDF 537 kb)

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Hack, M., Saghatelyan, A., de Chevigny, A. et al. Neuronal fate determinants of adult olfactory bulb neurogenesis. Nat Neurosci 8, 865–872 (2005). https://doi.org/10.1038/nn1479

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