Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity

Key Points

  • NG2 cells, or polydendrocytes, are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes and microglia. They can be identified by the expression of the NG2 proteoglycan, have a highly branched morphology and are distributed throughout the grey and white matter.

  • Polydendrocytes differentiate into oligodendrocytes in vitro and have often been equated with oligodendrocyte precursor cells (OPCs). However, it is now highly debated whether polydendrocytes are multipotential cells that can give rise to neurons and astrocytes as well as oligodendrocytes. Recent findings from in vivo fate-mapping studies provide insights into this issue.

  • Polydendrocytes have an important role in remyelination, as they have the ability to proliferate and differentiate after a demyelinating insult.

  • Recent findings have described the interaction of polydendrocytes with neurons. These findings include observations that polydendrocytes receive synaptic inputs from neurons and the role of polydendrocytes in axonal growth.

Abstract

NG2 cells (also known as polydendrocytes) are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes and microglia. They can be identified by the expression of the proteoglycan NG2, have a highly branched morphology and are distributed throughout the grey and white matter. They differentiate into oligodendrocytes in vitro and have often been equated with oligodendrocyte precursor cells. However, whether polydendrocytes are multipotential cells that can give rise to neurons and astrocytes as well as oligodendrocytes is now highly debated. Furthermore, electrophysiological studies indicate that polydendrocytes receive synaptic input from neurons, suggesting that they are integrated in the neural network. This Review highlights recent findings and unresolved questions related to the lineage and function of polydendrocytes in the CNS.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Development of polydendrocytes.
Figure 2: Hypothetical lineal relationship between polydendrocytes and other macroglia.
Figure 3: Events that occur in response to a demyelinating lesion in the corpus callosum.
Figure 4: Neuron–polydendrocyte synapses.

References

  1. Nishiyama, A. Polydendrocytes: NG2 cells with many roles in development and repair of the CNS. Neuroscientist 13, 62–76 (2007).

    CAS  PubMed  Article  Google Scholar 

  2. Nishiyama, A., Watanabe, M., Yang, Z. & Bu, J. Identity, distribution, and development of polydendrocytes: NG2-expressing glial cells. J. Neurocytol. 31, 437–455 (2002).

    CAS  PubMed  Article  Google Scholar 

  3. Levine, J. M. & Stallcup, W. B. Plasticity of developing cerebellar cells in vitro studied with antibodies against the NG2 antigen. J. Neurosci. 7, 2721–2731 (1987).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. Stallcup, W. B. & Beasley, L. Bipotential glial precursor cells of the optic nerve express the NG2 proteoglycan. J. Neurosci. 7, 2737–2744 (1987).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. Richardson, W. D., Pringle, N., Mosley, M. J., Westermark, B. & Dubois-Dalcq, M. A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell 53, 309–319 (1988).

    CAS  PubMed  Article  Google Scholar 

  6. Noble, M., Murray, K., Stroobant, P., Waterfield, M. D. & Riddle, P. Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature 333, 560–562 (1988).

    CAS  PubMed  Article  Google Scholar 

  7. Pringle, N. P., Mudhar, H. S., Collarini, E. J. & Richardson, W. D. PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage. Development 115, 535–551 (1992).

    CAS  PubMed  Article  Google Scholar 

  8. Pringle, N. P. & Richardson, W. D. A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage. Development 117, 525–533 (1993).

    CAS  PubMed  Article  Google Scholar 

  9. Spassky, N. et al. Single or multiple oligodendroglial lineages: a controversy. Glia 29, 143–148 (2000).

    CAS  PubMed  Article  Google Scholar 

  10. Fruttiger, M. et al. Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. Development 126, 457–467 (1999).

    CAS  PubMed  Article  Google Scholar 

  11. Nishiyama, A., Lin, X. H., Giese, N., Heldin, C. H. & Stallcup, W. B. Co-localization of NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells in the developing rat brain. J. Neurosci. Res. 43, 299–314 (1996).

    CAS  PubMed  Article  Google Scholar 

  12. Nishiyama, A., Yu, M., Drazba, J. A. & Tuohy, V. K. Normal and reactive NG2+ glial cells are distinct from resting and activated microglia. J. Neurosci. Res. 48, 299–312 (1997).

    CAS  PubMed  Article  Google Scholar 

  13. Komitova, M., Zhu, X., Serwanski, D. R. & Nishiyama, A. NG2 cells are distinct from neurogenic cells in the postnatal mouse subventricular zone. J. Comp. Neurol. (in the press).

  14. Dawson, M. R., Polito, A., Levine, J. M. & Reynolds, R. NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol. Cell. Neurosci. 24, 476–488 (2003).

    CAS  PubMed  Article  Google Scholar 

  15. Ozerdem, U., Grako, K. A., Dahlin-Huppe, K., Monosov, E. & Stallcup, W. B. NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev. Dyn. 222, 218–227 (2001).

    CAS  PubMed  Article  Google Scholar 

  16. Bignami, A., Eng, L. F., Dahl, D. & Uyeda, C. T. Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res. 43, 429–435 (1972).

    CAS  PubMed  Article  Google Scholar 

  17. Furuta, A., Rothstein, J. D. & Martin, L. J. Glutamate transporter protein subtypes are expressed differentially during rat CNS development. J. Neurosci. 17, 8363–8375 (1997).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. Polito, A. & Reynolds, R. NG2-expressing cells as oligodendrocyte progenitors in the normal and demyelinated adult central nervous system. J. Anat. 207, 707–716 (2005).

    PubMed  PubMed Central  Article  Google Scholar 

  19. Ghandour, M. S., Langley, O. K., Labourdette, G., Vincendon, G. & Gombos, G. Specific and artefactual cellular localizations of S 100 protein: an astrocyte marker in rat cerebellum. Dev. Neurosci. 4, 66–78 (1981).

    CAS  PubMed  Article  Google Scholar 

  20. Ludwin, S. K., Kosek, J. C. & Eng, L. F. The topographical distribution of S-100 and GFA proteins in the adult rat brain: an immunohistochemical study using horseradish peroxidase-labelled antibodies. J. Comp. Neurol. 165, 197–208 (1976).

    CAS  PubMed  Article  Google Scholar 

  21. Dyck, R. H., Van Eldick, L. J. & Cynader, M. S. Immunohistochemical localization of the S-100β protein in postnatal cat visual cortex: spatial and temporal patterns of expression in cortical and subcortical glia. Brain Res. Dev. Brain Res. 72, 181–192 (1993).

    CAS  PubMed  Article  Google Scholar 

  22. Deloulme, J. C. et al. Nuclear expression of S100B in oligodendrocyte progenitor cells correlates with differentiation toward the oligodendroglial lineage and modulates oligodendrocytes maturation. Mol. Cell. Neurosci. 27, 453–465 (2004).

    CAS  PubMed  Article  Google Scholar 

  23. Hachem, S., Aguirre, A., Vives, V., Marks, A., Gallo, V. & Legraverend, C. Spatial and temporal expression of S100B in cells of oligodendrocyte lineage. Glia 51, 181–197 (2005).

    Article  Google Scholar 

  24. Cenci di Bello, I., Dawson, M. R., Levine, J. M. & Reynolds, R. Generation of oligodendroglial progenitors in acute inflammatory demyelinating lesions of the rat brain stem is associated with demyelination rather than inflammation. J. Neurocytol. 28, 365–381 (1999).

    Article  Google Scholar 

  25. Dawson, M. R., Levine, J. M. & Reynolds, R. NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J. Neurosci. Res. 61, 471–479 (2000).

    CAS  PubMed  Article  Google Scholar 

  26. Bu, J., Akhtar, N. & Nishiyama, A. Transient expression of the NG2 proteoglycan by a subpopulation of activated macrophages in an excitotoxic hippocampal lesion. Glia 34, 296–310 (2001).

    CAS  PubMed  Article  Google Scholar 

  27. Jones, L. L., Sajed, D. & Tuszynski, M. H. Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition. J. Neurosci. 23, 9276–9288 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. McTigue, D. M., Wei, P. & Stokes, B. T. Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J. Neurosci. 21, 3392–3400 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. Levine, J. M., Stincone, F. & Lee, Y. S. Development and differentiation of glial precursor cells in the rat cerebellum. Glia 7, 307–321 (1993).

    CAS  PubMed  Article  Google Scholar 

  30. Peters, A. A fourth type of neuroglial cell in the adult central nervous system. J. Neurocytol. 33, 345–357 (2004). This study provides an ultrastructural confirmation that there is an abundant glial population in the mature CNS that is morphologically distinct from astrocytes, oligodendrocytes and microglia.

    PubMed  Article  Google Scholar 

  31. Karram, K. et al. NG2-expressing cells in the nervous system revealed by the NG2-EYFP-knockin mouse. Genesis 15 Oct 2008 (doi: 10.1002/dvg.20440). This paper describes the distribution of the reporter EYFP in the new transgenic mouse line in which EYFP was inserted into the Cspg4 locus.

    CAS  PubMed  Article  Google Scholar 

  32. Zhu, X., Bergles, D. E. & Nishiyama, A. NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development 135, 145–157 (2008). Fate mapping of polydendrocytes using NG2–Cre-transgenic mice showed that the predominant fate of these cells is to differentiate into oligodendrocytes and a subset of protoplasmic astrocytes in the grey matter.

    CAS  PubMed  Article  Google Scholar 

  33. Reynolds, R. & Hardy, R. Oligodendroglial progenitors labeled with the O4 antibody persist in the adult rat cerebral cortex in vivo. J. Neurosci. Res. 47, 455–470 (1997).

    CAS  PubMed  Article  Google Scholar 

  34. Kitada, M. & Rowitch, D. H. Transcription factor co-expression patterns indicate heterogeneity of oligodendroglial subpopulations in adult spinal cord. Glia 54, 35–46 (2006).

    PubMed  Article  Google Scholar 

  35. Ligon, K. L. et al. Development of NG2 neural progenitor cells requires Olig gene function. Proc. Natl Acad. Sci. USA 103, 7853–7858 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. Lu, Q. R. et al. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109, 75–86 (2002).

    CAS  PubMed  Article  Google Scholar 

  37. Zhou, Q. & Anderson, D. J. The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 109, 61–73 (2002).

    CAS  PubMed  Article  Google Scholar 

  38. Bu, J., Banki, A., Wu, Q. & Nishiyama, A. Increased NG2+ glial cell proliferation and oligodendrocyte generation in the hypomyelinating mutant shiverer. Glia 48, 51–63 (2004).

    PubMed  Article  Google Scholar 

  39. Horner, P. J. et al. Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J. Neurosci. 20, 2218–2228 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. Franklin, R. J. & Blakemore, W. F. Transplanting oligodendrocyte progenitors into the adult CNS. J. Anat. 190, 23–33 (1997).

    PubMed  PubMed Central  Article  Google Scholar 

  41. Zhu, X., Hill, R. A. & Nishiyama, A. NG2 cells generate oligodendrocytes and gray matter astrocytes in the spinal cord. Neuron Glia Biol. 13 Nov 2008 (doi:10.1017/S1740925X09000015).

    PubMed  Article  Google Scholar 

  42. Zhu, X., Komitova, M., Suzuki, R. & Nishiyama, A. Lack of neurogenesis from NG2 cells in olfactory bulb. Neuroscience Meeting Planner 455.2 (San Diego, 2007).

  43. Dimou, L., Simon, C., Takebayashi, H. & Gotz, M. Progeny of Olig2-expressing progenitors in the grey and white matter of the adult mouse cerebral cortex. J. Neurosci. 28, 10434–10442 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. Rivers, R. E. et al. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nature Neurosci. 11, 1392–1401 (2008). A carefully conducted study using PDGFRα–CreER-transgenic mice which demonstrated that polydendrocytes (PDGFRα-expressing cells) in the adult brain generate oligodendrocytes and a small number of neurons in the piriform cortex but not the olfactory bulb.

    CAS  PubMed  Article  Google Scholar 

  45. McCarthy, G. F. & Leblond, C. P. Radioautographic evidence for slow astrocyte turnover and modest oligodendrocyte production in the corpus callosum of adult mice infused with 3H-thymidine. J. Comp. Neurol. 271, 589–603 (1988).

    CAS  PubMed  Article  Google Scholar 

  46. Raff, M. C., Miller, R. H. & Noble, M. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303, 390–396 (1983).

    CAS  PubMed  Article  Google Scholar 

  47. Rao, M. S. & Mayer-Proschel, M. Glial-restricted precursors are derived from multipotent neuroepithelial stem cells. Dev. Biol. 188, 48–63 (1997).

    CAS  PubMed  Article  Google Scholar 

  48. Cahoy, J. D. et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264–278 (2008). A comprehensive transcriptional profiling of neurons, astrocytes and oligodendrocytes isolated from different postnatal stages.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. ffrench-Constant, C. & Raff, M. C. The oligodendrocyte-type-2 astrocyte cell lineage is specialized for myelination. Nature 323, 335–338 (1986).

    CAS  PubMed  Article  Google Scholar 

  50. Liu, Y. et al. Oligodendrocyte and astrocyte development in rodents: an in situ and immunohistological analysis during embryonic development. Glia 40, 25–43 (2002).

    PubMed  Article  Google Scholar 

  51. Nishiyama, A., Chang, A. & Trapp, B. D. NG2+ glial cells: a novel glial cell population in the adult brain. J. Neuropathol. Exp. Neurol. 58, 1113–1124 (1999).

    CAS  PubMed  Article  Google Scholar 

  52. Reynolds, R. et al. The response of NG2-expressing oligodendrocyte progenitors to demyelination in MOG-EAE and MS. J. Neurocytol. 31, 523–536 (2002).

    PubMed  Article  Google Scholar 

  53. Espinosa de los Monteros, A., Zhang, M. & de Vellis, J. O2A progenitor cells transplanted into the neonatal rat brain develop into oligodendrocytes but not astrocytes. Proc. Natl Acad. Sci. USA 90, 50–54 (1993).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. Groves, A. K. et al. Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. Nature 362, 453–455 (1993).

    CAS  PubMed  Article  Google Scholar 

  55. Franklin, R. J. M., Bayley, S. A., Milner, R., ffrench-Constant, C. & Blakemore, W. F. Differentiation of the O-2A progenitor cell line CG-4 into oligodendrocytes and astrocytes following transplantation into glia-deficient areas of CNS white matter. Glia 13, 39–44 (1995).

    CAS  PubMed  Article  Google Scholar 

  56. Windrem, M. S. et al. Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenically dysmyelinated brain. Nature Med. 10, 93–97 (2004).

    CAS  PubMed  Article  Google Scholar 

  57. Novak, A., Guo, C., Yang, W., Nagy, A. & Lobe, C. G. Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis 28, 147–155 (2000).

    CAS  PubMed  Article  Google Scholar 

  58. Cajal, S. R. Histology of the Nervous System (Oxford University Press, 1995).

    Google Scholar 

  59. Bushong, E. A., Martone, M. E., Jones, Y. Z. & Ellisman, M. H. Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J. Neurosci. 22, 183–192 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. Kessaris, N. et al. Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nature Neurosci. 9, 173–179 (2006). Demonstrates that at least three different sources of progenitor cells contribute to oligodendrogliogenesis in the forebrain and are functionally equivalent in their oligodendrogliogenic potential.

    CAS  PubMed  Article  Google Scholar 

  61. Levison, S. W., Young, G. M. & Goldman, J. E. Cycling cells in the adult rat neocortex preferentially generate oligodendroglia. J. Neurosci. Res. 57, 435–446 (1999).

    CAS  PubMed  Article  Google Scholar 

  62. Parnavelas, J. G. Glial cell lineages in the rat cerebral cortex. Exp. Neurol. 156, 418–429 (1999).

    CAS  PubMed  Article  Google Scholar 

  63. Malatesta, P. et al. Neuronal or glial progeny: regional differences in radial glia fate. Neuron 37, 751–764 (2003).

    CAS  PubMed  Article  Google Scholar 

  64. Voigt, T. Development of glial cells in the cerebral wall of ferrets: direct tracing of their transformation from radial glia into astrocytes. J. Comp. Neurol. 289, 74–88 (1989).

    CAS  PubMed  Article  Google Scholar 

  65. Fukuda, S., Kondo, T., Takebayashi, H. & Taga, T. Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway. Cell Death Differ. 11, 196–202 (2004).

    CAS  PubMed  Article  Google Scholar 

  66. Marshall, C. A., Novitch, B. G. & Goldman, J. E. Olig2 directs astrocyte and oligodendrocyte formation in postnatal subventricular zone cells. J. Neurosci. 25, 7289–7298 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. Setoguchi, T. & Kondo, T. Nuclear export of OLIG2 in neural stem cells is essential for ciliary neurotrophic factor-induced astrocyte differentiation. J. Cell Biol. 166, 963–968 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  68. Masahira, N. et al. 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. Dev. Biol. 293, 358–369 (2006).

    CAS  PubMed  Article  Google Scholar 

  69. Takebayashi, H. et al. 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. Mech. Dev. 99, 143–148 (2000).

    CAS  PubMed  Article  Google Scholar 

  70. Cai, J. et al. A crucial role for Olig2 in white matter astrocyte development. Development 134, 1887–1899 (2007). Using different Cre driver lines crossed to floxed Olig2 mice, Olig2 was deleted in different populations. Differential astrogliogenic effects of Olig2 deletion are seen in GFAP+ early stem cells and in Cnp + oligodendrocyte lineage cells.

    CAS  PubMed  Article  Google Scholar 

  71. Cheng, X. et al. Bone morphogenetic protein signaling and olig1/2 interact to regulate the differentiation and maturation of adult oligodendrocyte precursor cells. Stem Cells 25, 3204–3214 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. Kondo, T. & Raff, M. Chromatin remodeling and histone modification in the conversion of oligodendrocyte precursors to neural stem cells. Genes Dev. 18, 2963–2972 (2004). This paper extended the authors' earlier finding that isolated OPCs can be reprogrammed to turn into multipotent cells and described a role for chromatin remodelling in this conversion.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  73. Marin-Husstege, M. et al. Multiple roles of Id4 in developmental myelination: predicted outcomes and unexpected findings. Glia 54, 285–296 (2006).

    PubMed  Article  Google Scholar 

  74. Samanta, J. & Kessler, J. A. Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation. Development 131, 4131–4142 (2004).

    CAS  PubMed  Article  Google Scholar 

  75. Sauvageot, C. M. & Stiles, C. D. Molecular mechanisms controlling cortical gliogenesis. Curr. Opin. Neurobiol. 12, 244–249 (2002).

    CAS  PubMed  Article  Google Scholar 

  76. Hampton, D. W. et al. A potential role for bone morphogenetic protein signalling in glial cell fate determination following adult central nervous system injury in vivo. Eur. J. Neurosci. 26, 3024–3035 (2007). This article shows that noggin must be blocked before polydendrocytes can be transformed into astrocytes in a neocortical mechanical wound.

    PubMed  Article  Google Scholar 

  77. Alonso, G. NG2 proteoglycan-expressing cells of the adult rat brain: possible involvement in the formation of glial scar astrocytes following stab wound. Glia 49, 318–338 (2005).

    CAS  PubMed  Article  Google Scholar 

  78. Magnus, T. et al. Adult glial precursor proliferation in mutant SOD1G93A mice. Glia 56, 200–208 (2008).

    PubMed  Article  Google Scholar 

  79. Magnus, T. et al. Evidence that nucleocytoplasmic Olig2 translocation mediates brain-injury-induced differentiation of glial precursors to astrocytes. J. Neurosci. Res. 85, 2126–2137 (2007).

    CAS  PubMed  Article  Google Scholar 

  80. Schools, G. P., Zhou, M. & Kimelberg, H. K. Electrophysiologically “complex” glial cells freshly isolated from the hippocampus are immunopositive for the chondroitin sulfate proteoglycan NG2. J. Neurosci. Res. 73, 765–777 (2003).

    CAS  PubMed  Article  Google Scholar 

  81. Zhou, M., Schools, G. P. & Kimelberg, H. K. GFAP mRNA positive glia acutely isolated from rat hippocampus predominantly show complex current patterns. Mol. Brain Res. 76, 121–131 (2000).

    CAS  PubMed  Article  Google Scholar 

  82. Matthias, K. et al. Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. J. Neurosci. 23, 1750–1758 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  83. Ye, P., Bagnell, R. & D'Ercole, A. J. Mouse NG2+ oligodendrocyte precursors express mRNA for proteolipid protein but not its DM-20 variant: a study of laser microdissection-captured NG2+ cells. J. Neurosci. 23, 4401–4405 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. Zuo, Y. et al. Fluorescent proteins expressed in mouse transgenic lines mark subsets of glia, neurons, macrophages, and dendritic cells for vital examination. J. Neurosci. 24, 10999–11009 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  85. Domercq, M. & Matute, C. Expression of glutamate transporters in the adult bovine corpus callosum. Brain Res. Mol. Brain Res. 67, 296–302 (1999).

    CAS  PubMed  Article  Google Scholar 

  86. Paukert, M. & Bergles, D. E. Synaptic communication between neurons and NG2+ cells. Curr. Opin. Neurobiol. 16, 515–521 (2006).

    CAS  PubMed  Article  Google Scholar 

  87. Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000).

    CAS  PubMed  Article  Google Scholar 

  88. Zhuo, L. et al. hGFAP-cre transgenic mice for manipulation of glial and neuronal function in vivo. Genesis 31, 85–94 (2001).

    CAS  PubMed  Article  Google Scholar 

  89. Omlin, F. X. & Waldmeyer, J. Differentiation of neuron-like cells in cultured rat optic nerves: a neuron or common neuron-glia progenitor? Dev. Biol. 133, 247–253 (1989).

    CAS  PubMed  Article  Google Scholar 

  90. Kondo, T. & Raff, M. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289, 1754–1757 (2000).

    CAS  PubMed  Article  Google Scholar 

  91. Liu, A. et al. The glial or neuronal fate choice of oligodendrocyte progenitors is modulated by their ability to acquire an epigenetic memory. J. Neurosci. 27, 7339–7343 (2007). This paper showed that inhibiting histone deacetylation can convert OPCs into neuronal cells in vitro , but the identity of cells that are affected by valproate in vivo remains unclear.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  92. Belachew, S. et al. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J. Cell Biol. 161, 169–186 (2003). This paper, along with subsequently published papers from the same group (see references 95 and 96), demonstrated neuronal differentiation from polydendrocytes.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. Roy, N. S. et al. Identification, isolation, and promoter-defined separation of mitotic oligodendrocyte progenitor cells from the adult human subcortical white matter. J. Neurosci. 19, 9986–9995 (1999).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  94. Nunes, M. C. et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nature Med. 9, 439–447 (2003).

    CAS  PubMed  Article  Google Scholar 

  95. Aguirre, A. & Gallo, V. Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone. J. Neurosci. 24, 10530–10541 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  96. Aguirre, A. A., Chittajallu, R., Belachew, S. & Gallo, V. NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus. J. Cell Biol. 165, 575–589 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  97. Dayer, A. G., Cleaver, K. M., Abouantoun, T. & Cameron, H. A. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J. Cell Biol. 168, 415–427 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. Alvarez-Buylla, A., Seri, B. & Doetsch, F. Identification of neural stem cells in the adult vertebrate brain. Brain Res. Bull. 57, 751–758 (2002).

    PubMed  Article  Google Scholar 

  99. Platel, J.-C., Gordon, V., Heintz, T. & Bordey, A. GFAP-GFP neural progenitors are antigenically homogeneous and anchored in their enclosed mosaic niche. Glia 57, 66–78 (2008).

    Article  Google Scholar 

  100. Buffo, A. et al. Origin and progeny of reactive gliosis: a source of multipotent cells in the injured brain. Proc. Natl Acad. Sci. USA 105, 3581–3586 (2008). This study showed that, in contrast to the neurogenic potential of astrocytes in the mature brain, isolated polydendrocytes did not generate neurospheres.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  101. Lassmann, H., Bruck, W., Lucchinetti, C. & Rodriguez, M. Remyelination in multiple sclerosis. Mult. Scler. 3, 133–136 (1997).

    CAS  PubMed  Article  Google Scholar 

  102. Chandran, S. et al. Myelin repair: the role of stem and precursor cells in multiple sclerosis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 363, 171–183 (2008).

    CAS  PubMed  Article  Google Scholar 

  103. Smith, K. J. & McDonald, W. I. Spontaneous and mechanically evoked activity due to central demyelinating lesion. Nature 286, 154–155 (1980).

    CAS  PubMed  Article  Google Scholar 

  104. Chang, A., Nishiyama, A., Peterson, J., Prineas, J. & Trapp, B. D. NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J. Neurosci. 20, 6404–6412 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  105. Chang, A., Tourtellotte, W. W., Rudick, R. & Trapp, B. D. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N. Engl. J. Med. 346, 165–173 (2002).

    PubMed  Article  Google Scholar 

  106. Prineas, J. W. et al. Multiple sclerosis: oligodendrocyte proliferation and differentiation in fresh lesions. Lab. Invest. 61, 489–503 (1989).

    CAS  PubMed  Google Scholar 

  107. Solanky, M. et al. Proliferating oligodendrocytes are present in both active and chronic inactive multiple sclerosis plaques. J. Neurosci. Res. 65, 308–317 (2001).

    CAS  PubMed  Article  Google Scholar 

  108. Wolswijk, G. Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J. Neurosci. 18, 601–609 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  109. Bunge, M. B., Bunge, R. P. & Ris, H. Ultrastructural study of remyelination in an experimental lesion in adult cat spinal cord. J. Biophys. Biochem. Cytol. 10, 67–94 (1961).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  110. Carroll, W. M., Jennings, A. R. & Mastaglia, F. L. The origin of remyelinating oligodendrocytes in antiserum-mediated demyelinative optic neuropathy. Brain 113, 953–973 (1990).

    PubMed  Article  Google Scholar 

  111. Gensert, J. M. & Goldman, J. E. Endogenous progenitors remyelinate demyelinated axons in the adult CNS. Neuron 19, 197–203 (1997).

    CAS  PubMed  Article  Google Scholar 

  112. Keirstead, H. S., Levine, J. M. & Blakemore, W. F. Response of the oligodendrocyte progenitor cell population (defined by NG2 labelling) to demyelination of the adult spinal cord. Glia 22, 161–170 (1998).

    CAS  PubMed  Article  Google Scholar 

  113. Levine, J. M. & Reynolds, R. Activation and proliferation of endogenous oligodendrocyte precursor cells during ethidium bromide-induced demyelination. Exp. Neurol. 160, 333–347 (1999).

    CAS  PubMed  Article  Google Scholar 

  114. Armstrong, R. C., Le, T. Q., Frost, E. E., Borke, R. C. & Vana, A. C. Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter. J. Neurosci. 22, 8574–8585 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  115. Mason, J. L. et al. Mature oligodendrocyte apoptosis precedes IGF-1 production and oligodendrocyte progenitor accumulation and differentiation during demyelination/remyelination. J. Neurosci. Res. 61, 251–262 (2000).

    CAS  PubMed  Article  Google Scholar 

  116. Watanabe, M., Toyama, Y. & Nishiyama, A. Differentiation of proliferated NG2-positive glial progenitor cells in a remyelinating lesion. J. Neurosci. Res. 69, 826–836 (2002).

    CAS  PubMed  Article  Google Scholar 

  117. Levison, S. W. & Goldman, J. E. Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron 10, 201–212 (1993).

    CAS  PubMed  Article  Google Scholar 

  118. Nait-Oumesmar, B. et al. Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur. J. Neurosci. 11, 4357–4366 (1999).

    CAS  PubMed  Article  Google Scholar 

  119. Jackson, E. L. et al. PDGFRα-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 51, 187–199 (2006).

    CAS  PubMed  Article  Google Scholar 

  120. Menn, B. et al. Origin of oligodendrocytes in the subventricular zone of the adult brain. J. Neurosci. 26, 7907–7918 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  121. Blakemore, W. F., Gilson, J. M. & Crang, A. J. Transplanted glial cells migrate over a greater distance and remyelinate demyelinated lesions more rapidly than endogenous remyelinating cells. J. Neurosci. Res. 61, 288–294 (2000).

    CAS  PubMed  Article  Google Scholar 

  122. Franklin, R. J., Gilson, J. M. & Blakemore, W. F. Local recruitment of remyelinating cells in the repair of demyelination in the central nervous system. J. Neurosci. Res. 50, 337–344 (1997).

    CAS  PubMed  Article  Google Scholar 

  123. Penderis, J., Shields, S. A. & Franklin, R. J. Impaired remyelination and depletion of oligodendrocyte progenitors does not occur following repeated episodes of focal demyelination in the rat central nervous system. Brain 126, 1382–1391 (2003).

    PubMed  Article  Google Scholar 

  124. Mason, J. L. et al. Oligodendrocytes and progenitors become progressively depleted within chronically demyelinated lesions. Am. J. Pathol. 164, 1673–1682 (2004).

    PubMed  PubMed Central  Article  Google Scholar 

  125. Armstrong, R. C., Le, T. Q., Flint, N. C., Vana, A. C. & Zhou, Y. X. Endogenous cell repair of chronic demyelination. J. Neuropathol. Exp. Neurol. 65, 245–256 (2006).

    PubMed  Article  Google Scholar 

  126. Chari, D. M. Remyelination in multiple sclerosis. Int. Rev. Neurobiol. 79, 589–620 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  127. Franklin, R. J. Why does remyelination fail in multiple sclerosis? Nature Rev. Neurosci. 3, 705–714 (2002).

    CAS  Article  Google Scholar 

  128. Chittajallu, R., Aguirre, A. & Gallo, V. NG2-positive cells in the mouse white and grey matter display distinct physiological properties. J. Physiol. 561, 109–122 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  129. Karadottir, R., Hamilton, N. B., Bakiri, Y. & Attwell, D. Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter. Nature Neurosci. 11, 450–456 (2008). This paper describes heterogeneity among polydendrocytes in their expression of Na+ channels and shows that action potentials are generated in these cells in the white matter of early postnatal cerebellum.

    CAS  PubMed  Article  Google Scholar 

  130. Battiste, J. et al. Ascl1 defines sequentially generated lineage-restricted neuronal and oligodendrocyte precursor cells in the spinal cord. Development 134, 285–293 (2007).

    CAS  PubMed  Article  Google Scholar 

  131. Parras, C. M. et al. The proneural gene Mash1 specifies an early population of telencephalic oligodendrocytes. J. Neurosci. 27, 4233–4242 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  132. Bouslama-Oueghlani, L., Wehrle, R., Sotelo, C. & Dusart, I. Heterogeneity of NG2-expressing cells in the newborn mouse cerebellum. Dev. Biol. 285, 409–421 (2005).

    CAS  PubMed  Article  Google Scholar 

  133. Chari, D. M., Huang, W. L. & Blakemore, W. F. Dysfunctional oligodendrocyte progenitor cell (OPC) populations may inhibit repopulation of OPC depleted tissue. J. Neurosci. Res. 73, 787–793 (2003).

    CAS  PubMed  Article  Google Scholar 

  134. Irvine, K. A. & Blakemore, W. F. A different regional response by mouse oligodendrocyte progenitor cells (OPCs) to high-dose X-irradiation has consequences for repopulating OPC-depleted normal tissue. Eur. J. Neurosci. 25, 417–424 (2007).

    PubMed  Article  Google Scholar 

  135. Kressin, K., Kuprijanova, E., Jabs, R., Seifert, G. & Steinhauser, C. Developmental regulation of Na+ and K+ conductances in glial cells of mouse hippocampal brain slices. Glia 15, 173–187 (1995).

    CAS  PubMed  Article  Google Scholar 

  136. Steinhauser, C., Jabs, R. & Kettenmann, H. Properties of GABA and glutamate responses in identified glial cells of the mouse hippocampal slice. Hippocampus 4, 19–35 (1994).

    CAS  PubMed  Article  Google Scholar 

  137. Berger, T., Walz, W., Schnitzer, J. & Kettenmann, H. GABA- and glutamate-activated currents in glial cells of the mouse corpus callosum slice. J. Neurosci. Res. 31, 21–27 (1992).

    CAS  PubMed  Article  Google Scholar 

  138. Barres, B. A., Koroshetz, W. J., Swartz, K. J., Chun, L. L. Y. & Corey, D. P. Ion channel expression by white matter glia: the O-2A glial progenitor cell. Neuron 4, 507–524 (1990).

    CAS  PubMed  Article  Google Scholar 

  139. Sontheimer, H., Trotter, J., Schachner, M. & Kettenmann, H. Channel expression correlates with differentiation stage during the development of oligodendrocytes from their precursor cells in culture. Neuron 2, 1135–1145 (1989).

    CAS  PubMed  Article  Google Scholar 

  140. Bergles, D. E., Roberts, J. D., Somogyi, P. & Jahr, C. E. Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405, 187–191 (2000). The first demonstration of a neuron–polydendrocyte synapse and the first determination of the current characteristics of polydendrocytes.

    CAS  PubMed  Article  Google Scholar 

  141. Jabs, R. et al. Synaptic transmission onto hippocampal glial cells with hGFAP promoter activity. J. Cell Sci. 118, 3791–3803 (2005).

    CAS  PubMed  Article  Google Scholar 

  142. Lin, S. C. & Bergles, D. E. Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nature Neurosci. 7, 24–32 (2004).

    CAS  PubMed  Article  Google Scholar 

  143. Ge, W. P. et al. Long-term potentiation of neuron–glia synapses mediated by Ca2+-permeable AMPA receptors. Science 312, 1533–1537 (2006). This article shows potentiation of EPSCs in hippocampal polydendrocytes following theta-burst stimulation.

    CAS  PubMed  Article  Google Scholar 

  144. Lin, S. C. et al. Climbing fiber innervation of NG2-expressing glia in the mammalian cerebellum. Neuron 46, 773–785 (2005).

    CAS  PubMed  Article  Google Scholar 

  145. Mangin, J. M., Kunze, A., Chittajallu, R. & Gallo, V. Satellite NG2 progenitor cells share common glutamatergic inputs with associated interneurons in the mouse dentate gyrus. J. Neurosci. 28, 7610–7623 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  146. Kukley, M., Capetillo-Zarate, E. & Dietrich, D. Vesicular glutamate release from axons in white matter. Nature Neurosci. 10, 311–320 (2007). Describes the neuron–polydendrocyte synapse and suggests that clusters of vesicles in unmyelinated fibres might be a source of glutamate (see also reference 133).

    CAS  PubMed  Article  Google Scholar 

  147. Ziskin, J. L., Nishiyama, A., Rubio, M., Fukaya, M. & Bergles, D. E. Vesicular release of glutamate from unmyelinated axons in white matter. Nature Neurosci. 10, 321–330 (2007). Describes neuron–polydendrocyte synapses in the white matter and raises the question of the source of the glutamate (see also reference 132).

    CAS  PubMed  Article  Google Scholar 

  148. Karadottir, R., Cavelier, P., Bergersen, L. H. & Attwell, D. NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 438, 1162–1166 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  149. Wang, C. et al. Functional N-methyl-D-aspartate receptors in O-2A glial precursor cells: a critical role in regulating polysialic acid-neural cell adhesion molecule expression and cell migration. J. Cell Biol. 135, 1565–1581 (1996).

    CAS  PubMed  Article  Google Scholar 

  150. Micu, I. et al. NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature 439, 988–992 (2006).

    CAS  PubMed  Article  Google Scholar 

  151. Salter, M. G. & Fern, R. NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438, 1167–1171 (2005).

    CAS  PubMed  Article  Google Scholar 

  152. Kimelberg, H. K. The problem of astrocyte identity. Neurochem. Int. 45, 191–202 (2004).

    CAS  PubMed  Article  Google Scholar 

  153. Nishiyama, A., Yang, Z. & Butt, A. Astrocytes and NG2-glia: what's in a name? J. Anat. 207, 687–693 (2005).

    PubMed  PubMed Central  Article  Google Scholar 

  154. Zhou, M., Schools, G. P. & Kimelberg, H. K. Development of GLAST(+) astrocytes and NG2(+) glia in rat hippocampus CA1: mature astrocytes are electrophysiologically passive. J. Neurophysiol. 95, 134–143 (2006). This paper showed that polydendrocytes and GLAST+ astrocytes are functionally distinct cell populations, and that both cell types' current characteristics change during development.

    CAS  PubMed  Article  Google Scholar 

  155. Itoh, T. et al. AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes. J. Neurochem. 81, 390–402 (2002).

    CAS  PubMed  Article  Google Scholar 

  156. Canossa, M., Gartner, A., Campana, G., Inagaki, N. & Thoenen, H. Regulated secretion of neurotrophins by metabotropic glutamate group I (mGluRI) and Trk receptor activation is mediated via phospholipase C signalling pathways. EMBO J. 20, 1640–1650 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  157. Gudz, T. I., Komuro, H. & Macklin, W. B. Glutamate stimulates oligodendrocyte progenitor migration mediated via an αv integrin/myelin proteolipid protein complex. J. Neurosci. 26, 2458–2466 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  158. Yuan, X., Eisen, A. M., McBain, C. J. & Gallo, V. A role for glutamate and its receptors in the regulation of oligodendrocyte development in cerebellar tissue slices. Development 125, 2901–2914 (1998).

    CAS  PubMed  Article  Google Scholar 

  159. Kukley, M. et al. Glial cells are born with synapses. FASEB J. 22, 2957–2969 (2008).

    CAS  PubMed  Article  Google Scholar 

  160. Chen, Z. J., Ughrin, Y. & Levine, J. M. Inhibition of axon growth by oligodendrocyte precursor cells. Mol. Cell. Neurosci. 20, 125–139 (2002).

    CAS  PubMed  Article  Google Scholar 

  161. Ughrin, Y. M., Chen, Z. J. & Levine, J. M. Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth cone collapse. J. Neurosci. 23, 175–186 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  162. Tan, A. M., Colletti, M., Rorai, A. T., Skene, J. H. & Levine, J. M. Antibodies against the NG2 proteoglycan promote the regeneration of sensory axons within the dorsal columns of the spinal cord. J. Neurosci. 26, 4729–4739 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  163. de Castro, R. Jr, Tajrishi, R., Claros, J. & Stallcup, W. B. Differential responses of spinal axons to transection: influence of the NG2 proteoglycan. Exp. Neurol. 192, 299–309 (2005).

    CAS  PubMed  Article  Google Scholar 

  164. Yang, Z. et al. NG2 glial cells provide a favorable substrate for growing axons. J. Neurosci. 26, 3829–3839 (2006). Contrary to the commonly made prediction that polydendrocytes inhibit axonal growth because they express the inhibitory proteoglycan NG2 (see contrasting findings in references 162 and 163), this paper showed that they provide a favourable substrate for growing axons, even when NG2 levels are elevated, and that growing axons extensively contact polydendrocytes in vivo.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  165. McTigue, D. M., Tripathi, R. & Wei, P. NG2 colocalizes with axons and is expressed by a mixed cell population in spinal cord lesions. J. Neuropathol. Exp. Neurol. 65, 406–420 (2006).

    CAS  PubMed  Article  Google Scholar 

  166. Nishiyama, A., Dahlin, K. J., Prince, J. T., Johnstone, S. R. & Stallcup, W. B. The primary structure of NG2, a novel membrane-spanning proteoglycan. J. Cell Biol. 114, 359–371 (1991).

    CAS  PubMed  Article  Google Scholar 

  167. Stallcup, W. B., Beasley, L. & Levine, J. Cell-surface molecules that characterize different stages in the development of cerebellar interneurons. Cold Spring Harb. Symp. Quant. Biol. 48, 761–774 (1983).

    CAS  PubMed  Article  Google Scholar 

  168. Stallcup, W. B. The NG2 proteoglycan: past insights and future prospects. J. Neurocytol. 31, 423–435 (2002).

    CAS  PubMed  Article  Google Scholar 

  169. Karram, K., Chatterjee, N. & Trotter, J. NG2-expressing cells in the nervous system: role of the proteoglycan in migration and glial-neuron interaction. J. Anat. 207, 735–744 (2005).

    PubMed  PubMed Central  Article  Google Scholar 

  170. Chatterjee, N. et al. Interaction of syntenin-1 and the NG2 proteoglycan in migratory oligodendrocyte precursor cells. J. Biol. Chem. 283, 8310–8317 (2008).

    CAS  PubMed  Article  Google Scholar 

  171. Makagiansar, I. T., Williams, S., Mustelin, T. & Stallcup, W. B. Differential phosphorylation of NG2 proteoglycan by ERK and PKCα helps balance cell proliferation and migration. J. Cell Biol. 178, 155–165 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  172. Fukushi, J., Inatani, M., Yamaguchi, Y. & Stallcup, W. B. Expression of NG2 proteoglycan during endochondral and intramembranous ossification. Dev. Dyn. 228, 143–148 (2003).

    CAS  PubMed  Article  Google Scholar 

  173. Petrini, S. et al. Human melanoma/NG2 chondroitin sulfate proteoglycan is expressed in the sarcolemma of postnatal human skeletal myofibers. Abnormal expression in merosin-negative and Duchenne muscular dystrophies. Mol. Cell. Neurosci. 23, 219–231 (2003).

    CAS  PubMed  Article  Google Scholar 

  174. Kadoya, K., Fukushi, J., Matsumoto, Y., Yamaguchi, Y. & Stallcup, W. B. NG2 proteoglycan expression in mouse skin: altered postnatal skin development in the NG2 null mouse. J. Histochem. Cytochem. 56, 295–303 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  175. Schneider, S. et al.The AN2 protein is a novel marker for the Schwann cell lineage expressed by immature and nonmyelinating Schwann cells. J. Neurosci. 21, 920–933 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  176. Pluschke, G. et al. Molecular cloning of a human melanoma-associated chondroitin sulfate proteoglycan. Proc. Natl Acad. Sci. USA 93, 9710–9715 (1996).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  177. Wilson, S. S., Baetge, E. E. & Stallcup, W. B. Antisera specific for cell lines with mixed neuronal and glial properties. Dev. Biol. 83, 146–153 (1981).

    CAS  PubMed  Article  Google Scholar 

  178. Nishiyama, A., Lin, X. H. & Stallcup, W. B. Generation of truncated forms of the NG2 proteoglycan by cell surface proteolysis. Mol. Biol. Cell 6, 1819–1832 (1995).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  179. Heintz, N. BAC to the future: the use of bac transgenic mice for neuroscience research. Nature Rev. Neurosci. 2, 861–870 (2001).

    CAS  Article  Google Scholar 

  180. Yang, X. W., Model, P. & Heintz, N. Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome. Nature Biotechnol. 15, 859–865 (1997).

    CAS  Article  Google Scholar 

  181. Kuhlbrodt, K., Herbarth, B., Sock, E., Hermans-Borgmeyer, I. & Wegner, M. Sox10, a novel transcriptional modulator in glial cells. J. Neurosci. 18, 237–250 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  182. Olivier, C. et al. Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo. Development 128, 1757–1769 (2001).

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgements

The authors' work is funded by grants from the US National Institutes of Health, the National Science Foundation, the National Multiple Sclerosis Society, the Wadsworth Foundation and the Connecticut Stem Cell Research Program. The authors would like to thank B. Richardson, M. Gotz, L. Dimou and J. Trotter for sharing their unpublished results and helpful discussions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Akiko Nishiyama.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Related links

Related links

FURTHER INFORMATION

Akiko Nishiyama's homepage

Glossary

Oligodendrocyte progenitor cell

(OPC). A committed cell that generates oligodendrocytes. The terms 'NG2 cell' and 'OPC' are often used synonymously. In this article, the term OPC is used for cells whose identity as NG2-expressing cells was not examined.

Pulse-chase labelling

A technique used to study the synthesis and trafficking of macromolecules in cells. A tracer compound (the pulse), such as 5-bromo-2′-deoxyuridine (BrdU), is given to cells or animals over a short period of time so that it is incorporated into the molecules or cells of interest. The cells or animals are then allowed to survive for a period of time in the absence of the tracer (the chase period), after which they are analysed for the distribution of the label.

Cre recombinase

A site-specific DNA recombinase from the P1 bacteriophage that excises DNA sequences flanked by Cre target sequences (loxP) that are in the same orientation.

Type-2 astrocyte

A GFAP+A2B5+ stellate cell that arises in culture from an A2B5+ O–2A progenitor cell.

Oligodendrocyte–type-2 astrocyte (O–2A) progenitor cell

An A2B5+ bipotential glial progenitor cell that can give rise to both oligodendrocytes and type-2 astrocytes in culture. The term is now used synonymously with the more frequently used term 'OPC'.

Type-1 astrocyte

A GFAP+ A2B5− flat cell in culture. It is morphologically and antigenically distinct from the type-2 astrocyte.

Glial-restricted progenitor (GRP) cell

An A2B5+ progenitor cell from the embryonic spinal cord that can give rise to type-1 and type-2 astrocytes and oligodendrocytes but not to neurons in culture.

Protoplasmic astrocyte

A type of astrocyte in the grey matter that has a large number of relatively short radially oriented processes with numerous spiny branches. The term is used for cells in vivo, but their relation to the type-1 and type-2 astrocytes that are seen in culture is not known.

Radial glial cell

A cell that appears during embryonic development, has its cell body in the ventricular zone and has a radially spanning thin process that reaches the pial surface. Neurons migrate along the radial processes of radial glia in the developing neocortex. Radial glia can generate neurons as well as astrocytes.

Retroviral labelling

A lineage-tracing experiment that uses a retrovirus that encodes a reporter. Because the retrovirus is an RNA virus with a genome that is integrated into the host genome, the virus is passed on to the progeny of the infected cells and is not diluted by cell division. The host cells must be proliferating to be infected by the retrovirus.

Fibrous astrocyte

An astrocyte in the white matter that was originally called a 'fibrous cell' because of its long thin processes. The term is used for cells in vivo, but their relation to the type-1 and type-2 astrocytes that are seen in culture is not known.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nishiyama, A., Komitova, M., Suzuki, R. et al. Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10, 9–22 (2009). https://doi.org/10.1038/nrn2495

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2495

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing