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PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice

Nature Neuroscience volume 11, pages 1392–1401 (2008)Cite this article

Abstract

Platelet-derived growth factor α receptor (PDGFRA)/NG2–expressing glia are distributed throughout the adult CNS. They are descended from oligodendrocyte precursors (OLPs) in the perinatal CNS, but it is not clear whether they continue to generate myelinating oligodendrocytes or other differentiated cells during normal adult life. We followed the fates of adult OLPs in Pdgfra-creERT2/Rosa26-YFP double-transgenic mice and found that they generated many myelinating oligodendrocytes during adulthood; >20% of all oligodendrocytes in the adult mouse corpus callosum were generated after 7 weeks of age, raising questions about the function of the late-myelinating axons. OLPs also produced some myelinating cells in the cortex, but the majority of adult-born cortical cells did not appear to myelinate. We found no evidence for astrocyte production in gray or white matter. However, small numbers of projection neurons were generated in the forebrain, especially in the piriform cortex, which is the main target of the olfactory bulb.

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Figure 1: Antigenic properties of adult OLPs/NG2 cells.
Figure 2: Cumulative BrdU labeling of adult OLPs/NG2 cells in vivo.
Figure 3: PDGFRA+ adult OLPs generate differentiated oligodendrocyte lineage cells.
Figure 4: Evidence for myelin protein synthesis in adult-born oligodendrocytes.
Figure 5: Adult OLPs generate myelinating oligodendrocytes.
Figure 6: Adult OLPs do not generate astrocytes.
Figure 7: OLPs generate cortical projection neurons in vivo.
Figure 8: Morphologies of YFP-labeled neurons in the piriform cortex.

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Acknowledgements

We thank our colleagues in the Wolfson Institute for Biomedical Research for discussions, help and encouragement. Special thanks to M. Grist and U. Dennehy for expert technical assistance and to T. Mitsumori for helping to construct the Fgfr3-icreERT2 transgene. Thanks also to D. Attwell for critically reading the manuscript and L. Dimou and M. Götz for exchanging data before publication. L.E.R. was supported by a collaborative studentship from the Biotechnology and Biological Sciences Research Council and Eisai London Research Laboratories at University College London. F.J. held a Marie Curie Fellowship from the European Union. K.M.Y. is an Alzheimer's Society Fellow in Stem Cell Research. M.R. and A.W. hold studentships from The Wellcome Trust and K.P. has a studentship from the Medical Research Council. We are grateful to the Gatsby Foundation for the purchase of a two-photon microscope and to M. Häusser for providing access to it. This work was also supported by Programme grants from the Medical Research Council and The Wellcome Trust.

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Author notes

  1. Françoise Jamen & Anna Wade

    Present address: Present addresses: CNRS Institut de Neurobiologie Alfred Fessard, 91198 Gif-sur-Yvette, France (F.J.); University College London Institute of Neurology, Queen's Square, London WC1N 3BG, UK (A.W.).,

  2. Leanne E Rivers, Kaylene M Young, Matteo Rizzi and Françoise Jamen: These authors contributed equally to this work.

Authors and Affiliations

  1. Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK

    Leanne E Rivers, Kaylene M Young, Matteo Rizzi, Françoise Jamen, Konstantina Psachoulia, Anna Wade, Nicoletta Kessaris & William D Richardson

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Contributions

F.J. made the Pdgfra-creERT2 mice and performed preliminary characterization. L.E.R. analyzed the mice, made the initial observations of adult oligodendrogenesis and neurogenesis, and contributed quantification for Figures 1,2,3, 7 and Supplementary Figure 2. K.M.Y. extended the observations, carried out all of the confocal microscopy and in situ hybridization and contributed substantially to all of the experiments. A.W. quantified olfactory bulb neurogenesis. K.P. contributed to the BrdU cumulative label experiments and quantified neurogenesis. M.R. performed the cell-filling experiments and two-photon microscopy. K.M.Y., N.K. and W.D.R. devised and supervised the experiments. W.D.R. obtained funding and wrote the paper.

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Correspondence to William D Richardson.

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Rivers, L., Young, K., Rizzi, M. et al. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci 11, 1392–1401 (2008). https://doi.org/10.1038/nn.2220

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