Abstract
The adult mouse subependymal zone (SEZ) harbors neural stem cells that are thought to exclusively generate GABAergic interneurons of the olfactory bulb. We examined the adult generation of glutamatergic juxtaglomerular neurons, which had dendritic arborizations that projected into adjacent glomeruli, identifying them as short-axon cells. Fate mapping revealed that these originate from Neurog2- and Tbr2-expressing progenitors located in the dorsal region of the SEZ. Examination of the progenitors of these glutamatergic interneurons allowed us to determine the sequential expression of transcription factors in these cells that are thought to be hallmarks of glutamatergic neurogenesis in the developing cerebral cortex and adult hippocampus. Indeed, the molecular specification of these SEZ progenitors allowed for their recruitment into the cerebral cortex after a lesion was induced. Taken together, our data indicate that SEZ progenitors not only produce a population of adult-born glutamatergic juxtaglomerular neurons, but may also provide a previously unknown source of progenitors for endogenous repair.
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Change history
11 December 2009
In the version of this article initially published, the email address of one of the corresponding authors was misspelled. It should be magdalena.goetz@helmholtz-muenchen.de. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We would like to thank F. Bedogni for invaluable advice on methods and we are particularly grateful to Y. Yanagawa for the Gad67::gfp mice. We would also like to thank T. Simon-Ebert, A. Steiner, T. Öztürk and S. Nestel for excellent technical assistance and S. Bauer for retroviral production. We would also like to thank A. Saghatelyan for invaluable discussions and comments on the manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft, including the excellence cluster Center for Integrated Protein Science Munich, by European Transcriptome, Regulome and Cellular Commitment Consortium from the European Union and the Bundesministerium für Bildung und Forschung to M.G., and the Bavarian State Ministry of Sciences, Research and the Arts (ForNeuroCell) to B.B. and M.G. E.W. was supported by a fellowship from the Medical Research Council, I.O. by a fellowship from the John & Lucille van Geest Foundation and O.R. by a grant from the Dr. Scholl Foundation. Research in the laboratory of F.G. is supported by funds from the Medical Research Council and grants from the European Commission Research and Technological Development program. C.P. is presently supported by an AVENIR-contract from Institut national de la santé et de la recherché mèdicale and Fondation de France. R.D.H. is supported by a Heart and Stroke Fund of Canada Research Fellowship. Work done in the laboratory of R.F.H. was supported by grants from the US National Institutes of Health (R01 NS050248 and R01 MH080766).
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M.S.B., O.R. and R.D.H. made the original observation of glutamatergic progenitors in the SEZ. M.S.B. conducted most of the experiments. J.N., E.W., O.R. and R.D.H. conducted experiments crucial for the identification of adult-generated glutamatergic neurons in the olfactory bulb. I.O. and R.Y. contributed to experiments using Neurog2+/gfp and Tbr2BAC-gfp mice, respectively. A.L. and S.G. designed and produced the viral vectors. F.E. and G.S. provided the Gad65-gfp mice. C.P. contributed with experiments using Ngn2+/gfp and Mash1BAC-gfp mice. F.G. provided the Neurog2gfp/+ and E1–Neurog2-cre mice. M.F. designed the electron-microscopy experiments and analyzed the data. B.B. designed and conducted all of the electrophysiological experiments. R.F.H., O.R. and M.G. supervised the project and designed experiments. M.G. wrote the manuscript. M.S.B., B.B., R.D.H., R.F.H. and O.R. contributed to the writing of the manuscript.
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Brill, M., Ninkovic, J., Winpenny, E. et al. Adult generation of glutamatergic olfactory bulb interneurons. Nat Neurosci 12, 1524–1533 (2009). https://doi.org/10.1038/nn.2416
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DOI: https://doi.org/10.1038/nn.2416
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