Skip to main content

NG2 cells generate oligodendrocytes and gray matter astrocytes in the spinal cord

  • Xiaoqin Zhu (a1), Robert A. Hill (a1) and Akiko Nishiyama (a1)

NG2 cells represent a unique glial cell population that is distributed widely throughout the developing and adult CNS and is distinct from astrocytes, mature oligodendrocytes and microglia. The ability of NG2 cells to differentiate into myelinating oligodendrocytes has been documented in vivo and in vitro. We reported recently that NG2 cells in the forebrain differentiate into myelinating oligodendrocytes but into a subpopulation of protoplasmic astrocytes (Zhu et al., 2008). However, the in vivo fate of NG2 cells in the spinal cord and cerebellum has remained unknown. To investigate the fate of NG2 cells in caudal central nervous system (CNS) regions in vivo, we examined the phenotype of cells that express EGFP in mice that are double transgenic for NG2CreBAC and the Cre reporter Z/EG. The fate of NG2 cells can be studied in these mice by permanent expression of EGFP in cells that have undergone Cre-mediated recombination in NG2 cells. We find that NG2 cells give rise to oligodendrocytes in both gray and white matter of the spinal cord and cerebellum, and to protoplasmic astrocytes in the gray matter of the spinal cord. However, NG2 cells do not give rise to astrocytes in the white matter of the spinal cord and cerebellum. These observations indicate that NG2 cells serve as precursor cells for oligodendrocytes and a subpopulation of protoplasmic astrocytes throughout the rostrocaudal axis of the CNS.

Corresponding author
Correspondence should be addressed to: Xiaoqin Zhu and Akiko Nishiyama, Department of Physiology and Neurobiology, University of Connecticut, 75 North Eagleville Road, Unit-3156, Storrs, CT 06269-3156, USA phone: +1 860 486 1694 fax: +1 860 486 3303 emails:;
Hide All
Barry D. and McDermott K. (2005) Differentiation of radial glia from radial precursor cells and transformation into astrocytes in the developing rat spinal cord. Glia 50, 187197.
Bhat R.V., Axt K.J., Fosnaugh J.S., Smith K.J., Johnson K.A., Hill D.E. et al. (1996) Expression of the APC tumor suppressor protein in oligodendroglia. Glia 17, 169174.
Bu J., Banki A., Wu Q. and Nishiyama A. (2004) Increased NG2(+) glial cell proliferation and oligodendrocyte generation in the hypomyelinating mutant shiverer. Glia 48, 5163.
Cai J., Qi Y., Hu X., Tan M., Liu Z., Zhang J. et al. (2005) Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron 45, 4153.
Choi B.H. and Kim R.C. (1984) Expression of glial fibrillary acidic protein in immature oligodendroglia. Science 223, 407409.
Dawson M.R., Levine J.M. and Reynolds R. (2000) NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? Journal of Neuroscience Research 61, 471479.
Dawson M.R., Polito A., Levine J.M. and Reynolds R. (2003) NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Molecular and Cellular Neuroscience 24, 476488.
Fogarty M., Richardson W.D. and Kessaris N. (2005) A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord. Development 132, 19511959.
Fruttiger M., Karlsson L., Hall A.C., Abramsson A., Calver A.R., Bostrom H. et al. (1999) Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. Development 126, 457467.
Hirano M. and Goldman J.E. (1988) Gliogenesis in rat spinal cord: evidence for origin of astrocytes and oligodendrocytes from radial precursors. Journal of Neuroscience Research 21, 155167.
Horner P.J., Power A.E., Kempermann G., Kuhn H.G., Palmer T.D., Winkler J. et al. (2000) Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. Journal of Neuroscience 20, 22182228.
Kessaris N., Fogarty M., Iannarelli P., Grist M., Wegner M. and Richardson W.D. (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nature Neuroscience 9, 173179.
Leber S.M., Breedlove S.M. and Sanes J.R. (1990) Lineage, arrangement, and death of clonally related motoneurons in chick spinal cord. Journal of Neuroscience 10, 24512462.
Levine J.M. and Stallcup W.B. (1987) Plasticity of developing cerebellar cells in vitro studied with antibodies against the NG2 antigen. Journal of Neuroscience 7, 27212731.
Ligon K.L., Kesari S., Kitada M., Sun T., Arnett H.A., Alberta J.A. et al. (2006) Development of NG2 neural progenitor cells requires Olig gene function. Proceedings of the National Academy of Sciences of the U.S.A. 103, 78537858.
Liu Y., Wu Y., Lee J.C., Xue H., Pevny L.H., Kaprielian Z. et al. (2002) Oligodendrocyte and astrocyte development in rodents: an in situ and immunohistological analysis during embryonic development. Glia 40, 2543.
Lu Q.R., Sun T., Zhu Z., Ma N., Garcia M., Stiles C.D. et al. (2002) Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109, 7586.
Magnus T., Carmen J., Deleon J., Xue H., Pardo A.C., Lepore A.C. et al. (2008) Adult glial precursor proliferation in mutant SOD1G93A mice. Glia 56, 200208.
Masahira N., Takebayashi H., Ono K., Watanabe K., Ding L., Furusho M. et al. (2006) Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells. Developmental Biology 293, 358369.
McLean I.W. and Nakane P.K. (1974) Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. Journal of Histochemistry and Cytochemistry 22, 10771083.
McTigue D.M., Horner P.J., Stokes B.T. and Gage F.H. (1998) Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. Journal of Neuroscience 18, 53545365.
Misson J.P., Edwards M.A., Yamamoto M. and Caviness V.S. Jr. (1988) Identification of radial glial cells within the developing murine central nervous system: studies based upon a new immunohistochemical marker. Brain Research Developmental Brain Research 44, 95108.
Nishiyama A. (2007) Polydendrocytes: NG2 cells with many roles in development and repair of the CNS. Neuroscientist 13, 6276.
Novak A., Guo C., Yang W., Nagy A. and Lobe C.G. (2000) Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis 28, 147155.
Raff M.C., Miller R.H. and Noble M. (1983) A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303, 390396.
Rao M.S. and Mayer-Proschel M. (1997) Glial-restricted precursors are derived from multipotent neuroepithelial stem cells. Developmental Biology 188, 4863.
Richardson W.D., Smith H.K., Sun T., Pringle N.P., Hall A. and Woodruff R. (2000) Oligodendrocyte lineage and the motor neuron connection. Glia 29, 136142.
Schmechel D.E. and Rakic P. (1979) A Golgi study of radial glial cells in developing monkey telencephalon: morphogenesis and transformation into astrocytes. Anatomy and Embryology 156, 115152.
Spassky N., Olivier C., Perez-Villegas E., Goujet-Zalc C., Martinez S., Thomas J. et al. (2000) Single or multiple oligodendroglial lineages: a controversy. Glia 29, 143148.
Stallcup W.B. and Beasley L. (1987) Bipotential glial precursor cells of the optic nerve express the NG2 proteoglycan. Journal of Neuroscience 7, 27372744.
Takebayashi H., Yoshida S., Sugimori M., Kosako H., Kominami R., Nakafuku M. et al. (2000) Dynamic expression of basic helix-loop-helix Olig family members: implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3. Mechanisms of Development 99, 143148.
Vallstedt A., Klos J.M. and Ericson J. (2005) Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron 45, 5567.
Watanabe M., Toyama Y. and Nishiyama A. (2002) Differentiation of proliferated NG2-positive glial progenitor cells in a remyelinating lesion. Journal of Neuroscience Research 69, 826836.
Yang X.W., Model P. and Heintz N. (1997) Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome. Nature Biotechnology 15, 859865.
Zhou Q. and Anderson D.J. (2002) The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 109, 6173.
Zhu X., Bergles D.E. and Nishiyama A. (2008) NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development 135, 145157.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Neuron Glia Biology
  • ISSN: 1740-925X
  • EISSN: 1741-0533
  • URL: /core/journals/neuron-glia-biology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 9
Total number of PDF views: 44 *
Loading metrics...

Abstract views

Total abstract views: 368 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st November 2017. This data will be updated every 24 hours.