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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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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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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DOI: https://doi.org/10.1038/nn1479
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