Journal of Neurocytology

, Volume 31, Issue 6–7, pp 437 ppl=–455 | Cite as

Identity, distribution, and development of polydendrocytes: NG2-expressing glial cells

  • Akiko Nishiyama
  • Masahiko Watanabe
  • Zhongshu Yang
  • Jie Bu


Cells that express the NG2 proteoglycan (NG2+ cells) comprise a unique population of glial cells in the central nervous system. While there is no question that some NG2+ cells differentiate into oligodendrocytes during development, the persistence of numerous NG2+ cells in the mature CNS has raised questions about their identity, relation to other CNS cell types, and functions besides their progenitor role. NG2+ cells also express the alpha receptor for platelet-derived growth factor (PDGF αR), a receptor that mediates oligodendrocyte progenitor proliferation during development. Antigenically, NG2+ cells are distinct from fibrous and protoplasmic astrocytes, resting microglia, and mature oligodendrocytes. Therefore, we propose the term polydendrocytesto refer to all NG2-expressing glial cells in the CNS parenchyma. This distinguishes them from the classical glial cell types and identifies them as the fourth major glial population in the CNS. Recent observations suggest that polydendrocytes are complex cells that physically and functionally interact with other cell types in the CNS. Committed oligodendrocyte progenitor cells arise from restricted foci in the ventral ventricular zone in both spinal cord and brain. It remains to be clarified whether there are multiple sources of oligodendrocytes, and if so whether polydendrocytes (NG2+ cells) represent progenitor cells of all oligodendrocyte lineages. Proliferation of NG2+ cells during early development appears to be dependent on PDGF, but the regulatory mechanisms that govern NG2+ cell proliferation in the mature CNS remain unknown. Pulse-chase labeling with bromodeoxyuridine indicates that polydendrocytes that proliferate in the postnatal spinal cord differentiate into oligodendrocytes. Novel experimental approaches are being developed to further elucidate the functional properties and differentiation potential of polydendrocytes.


  1. Acklin, S. E.& Van Der Kooy, D.(1993) Clonal Heterogeneity in the germinal zone of the developing rat telencephalon. Development 118, 175–192.Google Scholar
  2. Arnett, H. A., Mason, J., Marino, M., Suzuki, K., Matsushima, G. K.& Ting, J. P.(2001) TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat. Neurosci. 4, 1116–1122.Google Scholar
  3. Austyn, J. M.& Gordon, S.(1981) F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur. J. Immunol. 11, 805–815.Google Scholar
  4. Barres, B. A., Koroshetz, W. J., Swartz, K. J., Chun, L. L. Y.& Corey, D. P.(1990) Ion channel expression by white matter glia: The O-2A glial progenitor cell. Neuron 4, 507–524.Google Scholar
  5. Bergles, D. E., Roberts, J. D., Somogyi, P.& Jahr, C. E.(2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405, 187–191.Google Scholar
  6. Birling, M. C.& Price, J.(1998) A study of the potential of the embryonic rat telencephalon to generate oligodendrocytes. Dev. Biol. 193, 100–113.Google Scholar
  7. Borges, K., Ohlemeyer, C., Trotter, J.& Kettenmann, H.(1994) AMPA/kainate receptor activation in murine oligodendrocyte precursor cells leads to activation of a cation conductance, calcium influx and blockade of delayed rectifying K+channels. Neuroscience 63, 135–149.Google Scholar
  8. Bu, J., Akhtar, N.& Nishiyama, A.(2001) Transient expression of the NG2 proteoglycan by a subpopulation of activated macrophages in an excitotoxic hippocampal lesion. Glia 34, 296–310.Google Scholar
  9. Bu, J., Banki, A., Wu, Q.& Nishiyama, A.Increased proliferation and delayed differentiation of NG2-positive glial progenitor cells in the hypomyelinating mutant shiverer. Abstr. Soc. Neurosci. 47, 9.Google Scholar
  10. Bunge, M. B., Bunge, R. P.& Pappas, G. D.(1962) Electron microscopic demonstration of connections between glia and the myelin sheath in the developingmammalian central nervous system. Journal of Cell Biology 12, 448–453.Google Scholar
  11. Bushong, E. A., Martone, M. E., Jones, Y. Z.& Ellisman, M. H.(2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J. Neurosci. 22, 183–192.Google Scholar
  12. Butt, A. M., Colquhoun, K.& Berry, M.(1994a) Confocal imaging of glial cells in the intact rat optic nerve. Glia 10, 315–322.Google Scholar
  13. Butt, A. M., Colquhoun, K., Tutton, M.& Berry, M.(1994b) Three-dimensional morphology of astrocytes and oligodendrocytes in the intact mouse optic nerve. Journal of Neurocytology 23, 469–485.Google Scholar
  14. Butt, A. M., Duncan, A., Hornby, M. F., Kirvell, S. L., Hunter, A., Levine, J. M.& Berry, M.(1999) Cells expressing the NG2 antigen contact nodes of Ranvier in adult CNS white matter. Glia 26, 84–91.Google Scholar
  15. Calver, A. R., Hall, A. C., Yu, W.-P., Walsh, F. S., Heath, J. K., Betsholtz, C.& Richardson, W. D.(1998) Oligodendrocyte population dynamics and the role of PDGF in vivo. Neuron 20, 869–882.Google Scholar
  16. Cannoll, P. D., Musacchio, J. M., Hardy, R., Reynolds, R., Marchionni, M. A.& Salzer, J. L.(1996) GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors. Neuron 17, 229–243.Google Scholar
  17. Carroll, W. M., Jennings, A. R.& Ironside, L. J.(1998) Identification of the adult resting progenitor cell by autoradiographic tracking of oligodendrocyte precursors in experimental CNS demyelination. Brain 121, 293–302.Google Scholar
  18. Cenci Di Bello, I., Dawson, M. R., Levine, J. M.& Reynolds, R.(1999) 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.Google Scholar
  19. Chari, D. M.& Blakemore, W. F.(2002) Efficient recolonisation of progenitor-depleted areas of the CNS by adult oligodendrocyte progenitor cells. Glia 37, 307–313.Google Scholar
  20. Colello, R. J., Devey, L. R., Imperato, E.& Pott, U.(1995) The chronology of oligodendrocyte differentiation in the rat optic nerve: Evidence for a signaling step initiating myelination in the CNS. J. Neurosci. 15, 7665–7672.Google Scholar
  21. Cornell-Bell, A. H., Finkbeiner, S. M., Cooper, M. S.& Smith, S. J.(1990) Glutamate induces calcium waves in cultured astrocytes: Long-range glial signaling. Science 247, 470–473.Google Scholar
  22. Dawson, M. R., Levine, J. M.& Reynolds, R.(2000) NG2-expressing cells in the central nervous system: Are they oligodendroglial progenitors? J. Neurosci. Res. 61, 471–479.Google Scholar
  23. Diers-Fenger, M., Kirchhoff, F., Kettenmann, H., Levine, J. M.& Trotter, J.(2001) AN2/NG2 protein-expressing glial progenitor cells in the murine CNS: Isolation, differentiation, and association with radial glia. Glia 34, 213–228.Google Scholar
  24. Dijkstra, C. D., Dopp, E. A., Joling, P.& Kraal, G.(1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: Distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 54, 589–599.Google Scholar
  25. Dou, C. L.& Levine, J. M.(1994) Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan. Journal of Neuroscience 14, 7616–7628.Google Scholar
  26. Dou, C. L.& Levine, J. M.(1995) Differential effects of glycosaminoglycans on neurite growth on laminin and L1 substrates. Journal of Neuroscience 15, 8053–8066.Google Scholar
  27. Dyck, R. H., Van Eldick, L. J.& Cynader, M. S.(1993) Immunohistochemical localization of the S-100b protein in postnatal cat visual cortex: Spatial and temporal patterns of expression in cortical and subcortical glia. Developmental Brain Research 72, 181–192.Google Scholar
  28. Eisenbarth, G. S., Walsh, F. S.& Nirenberg, M.(1979) Monoclonal antibody to a plasma membrane antigen of neurons. Proceedings of the National Academy of Sciences of the USA 76, 4913–4917.Google Scholar
  29. Ellison, J. A.& De Vellis, J.(1994) Platelet-derived growth factor receptor is expressed by cells in the early oligodendrocyte lineage. Journal of Neuroscience Research 37, 116–128.Google Scholar
  30. Ellison, J. A.& De Vellis, J.(1995)Amoeboidmicroglia expressing GD3 ganglioside are concentrated in regions of oligodendrogenesis during development of the rat corpus callosum. Glia 14, 123–132.Google Scholar
  31. Eriksson, A., Siegbahn, A., Westrermark, B., Heldin, C. H.& Claesson-Welsh, L.(1992) PDGF a-and b-receptors activate unique and common signal transduction pathways.EMBOJournal 11, 543–550.Google Scholar
  32. Espinosa De Los Monteros, A., Zhang, M.& de Vellis, J.(1993) O2A progenitor cells transplanted into the neonatal rat brain develop into oligodendrocytes but not astrocytes. Proceedings of the National Academy of Sciences of the USA 90, 50–54.Google Scholar
  33. Fernandez, P. A., Tang, D. G., Cheng, L., Prochiantz, A., Mudge, A. W.& Raff, M. C.(2000) Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve. Neuron 28, 81–90.Google Scholar
  34. Ffrench-Constant, C., Miller, R. H., Burne, J. F.& Raff, M. C.(1988) Evidence that migratory oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells are kept out of the rat retina by a barrier at the eye-end of the optic nerve. Journal of Neurocytology 17, 13–23.Google Scholar
  35. Fidler, P. S., Schuette, K., Asher, R. A., Dobbertin, A., Thornton, S. R., Callepatino, Y., Muir, E., Levine, J. M., Geller, H. M., Rogers, J. H., Faissner, A.& Fawcett, J. W.(1999) Comparing astrocytic cell lines that are inhibitory or permissive for axon growth: The major axon-inhibitory proteoglycan is NG2. Journal of Neuroscience 19, 8778–8788.Google Scholar
  36. Fields, R. D.& Stevens, B.(2000) ATP: An extracellular signaling molecule between neurons and glia. Trends Neurosci. 23, 625–633.Google Scholar
  37. Franklin, R. J. M., Bayley, S. A., Milner, R., Ffrench-Constant, C.& Blakemore, W. F.(1995) Differentiation of theO-2Aprogenitor cell lineCG-4 into oligodendrocytes and astrocytes following transplantation into glia-deficient areas of CNS white matter. Glia 13, 39–44.Google Scholar
  38. Franklin, R. J.& Blakemore, W. F.(1997)Transplanting oligodendrocyte progenitors into the adult CNS. J. Anat. 190, 23–33.Google Scholar
  39. Fruttiger, M., Calver, A. R., Kruger, W. H., Mudhar, H. S., Michalovich, D., Takakura, N., Nishikawa, S.-I.& Richardson, W. D.(1996) PDGF mediates a neuron-astrocyte interaction in the developing retina. Neuron 17, 1117–1131.Google Scholar
  40. Fruttiger, M., Karlsson, L., Hall, A. C., Abramsson, A., Calver, A. R., Bostrom, H., Willetts, K., Bertold, C. H., Heath, J. K., Betsholtz, C.& Richardson, W. D.(1999) Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. Development 126, 457–467.Google Scholar
  41. Fruttiger, M., Calver, A. R.& Richardson, W. D.(2000) Platelet-derived growth factor is constitutively secreted from neuronal cell bodies but not from axons. Curr. Biol. 10, 1283–1286.Google Scholar
  42. Fu, H., Qi, Y., Tan, M., Cai, J., Takebayashi, H., Nakafuku, M., Richardson, W.& Qiu, M.(2002) Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation. Development 129, 681–693.Google Scholar
  43. Galileo, D. S., Gray, G. E., Owens, G. C., Majors, J.& Sanes, J. R.(1990) Neurons and glia arise from a common progenitor in chicken optic tectum: Demonstration with two retroviruses and cell type-specific antibodies. Proceedings of the National Academy of Sciences of the USA 87, 458–462.Google Scholar
  44. Gallo, V., Zhou, J. M., Mcbain, C. J., Wright, P., Knutson, P. L.& Armstrong, R. C.(1996) Oligodendrocyte progenitor cell proliferation and lineage progression are regulated by glutamate receptor-mediated K+channel block. Journal of Neuroscience 16, 2659–2670.Google Scholar
  45. Gard, A. L.& Pfeiffer, S. E.(1990) Two proliferative stages of the oligodendrocyte lineage (A2B5+O4?and O4+GalC?) under different mitogenic control. Neuron 5, 615–625.Google Scholar
  46. Gensert, J. M.& Goldman, J. E.(1997) Endogenous progenitors remyelinate demyelinated axons in the adult CNS. Neuron 19, 197–203.Google Scholar
  47. Grako, K.& Stallcup, W. B.(1995) Participation of the NG2 proteoglycan in rat aortic smooth muscle cell responses to pletelet-derived growth factor. Experimental Cell Research 22, 231–240.Google Scholar
  48. Groves, A. K., Barnett, S. C., Franklin, R. J. M., Crang, A. J., Mayer, M., Blakemore, W. F.& Noble, M.(1993) Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. Nature 362, 453–455.Google Scholar
  49. Hall, A., Giese, N. A.& Richardson, W. D.(1996) Spinal cord oligodendrocytes develop from ventrally derived progenitor cells that expressPDGFalpha-receptors. Development 122, 4085–4094.Google Scholar
  50. Hayes, C. E.& Goldstein, I. J.(1974) An ?-Dgalactosyl-binding lectin from Bandeiraea simplicifoliaseeds. J. Biol. Chem. 249, 1904–1914.Google Scholar
  51. He, W., Ingraham, C., Rising, L., Goderie, S.& Temple, S.(2001) Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis. J. Neurosci 21, 8854–8862.Google Scholar
  52. Jerrera, J., Yang, H., Zhang, S.-C., Proschel, C., Tresco, P., Duncan, I. D., Luskin, M.& Mayer-Proschel, M.(2001) Embryonic-derived glial-restricted precursor cells (GRP cells) can differentiate into astrocytes and oligodendrocytes in vivo. Exp. Neurol. 171, 11–21.Google Scholar
  53. Hinks, G. L., Chari, D. M., O'leary, M. T., Zhao, C., Keirstead, H. S., Blakemore, W. F.& Franklin, R. J.(2001) Depletion of endogenous oligodendrocyte progenitors rather than increased availability of survival factors is a likely explanation for enhanced survival of transplanted oligodendrocyte progenitors in X-irradiated compared to normal CNS. Neuropathol. Appl. Neurobiol. 27, 59–67.Google Scholar
  54. Horner, P. J., Power, A. E., Kempermann, G., Kuhn, H. G., Palmer, T. D., Winkler, J., Thal, L. J.& Gage, F. H.(2000) Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J. Neurosci. 20, 2218–2228.Google Scholar
  55. Hutchins, J. B.& Jefferson, V. E.(1992) Developmental distribution of platelet-derived growth factor in the mouse central nervous system. Developmental Brain Research 67, 121–135.Google Scholar
  56. Jessell, T. M.(2000) Neuronal specification in the spinal cord: Inductive signals and transcriptional codes. Nat. Rev. Genet. 1, 20–29.Google Scholar
  57. Jones, L. L., Yamaguchi, Y., Stallcup, W. B.& Tuszynski, M. H.(2002) NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J. Neurosci. 22, 2792–2803.Google Scholar
  58. Keirstead, H. S., Levine, J. M.& Blakemore, W. F. (1998) Response of the oligodendrocyte progenitor cell population (defined by NG2 labelling) to demyelination of the adult spinal cord. Glia 22, 161–170.Google Scholar
  59. Kessaris, N., Pringle, N.& Richardson, W. D.(2001) Ventral neurogenesis and the neuron-glial switch. Neuron 31, 677–680.Google Scholar
  60. Knutson, P., Ghiani, C. A., Zhou, J.-M., Gallo, V.& McBain, C. J.(1997) K+channel expression and cell proliferation are regulated by intracellular sodium and membrane depolarization in oligodendrocyte progenitor cells. Journal of Neuroscience 17, 2669–2682.Google Scholar
  61. Kressin, K., Kuprijanova, E., Jabs, R., Seifert, G.& Steinhauser, C.(1995) Developmental regulation of Na+and K+conductances in glial cells of mouse hippocampal brain slices. Glia 15, 173–187.Google Scholar
  62. Kriegler, S.& Chiu, S. Y.(1993) Calcium signaling of glial cells along mammalian axons. J. Neurosci. 13, 4229–4245.Google Scholar
  63. Kuffler, S. W.& Nicholls, J. G.(1966) The physiology of neuroglial cells. Ergeb. Physiol. 57, 1–90.Google Scholar
  64. Kuffler, S. W.& Nicholls, J. G.(1966) The physiology of neuroglial cells. Ergeb. Physiol. 57, 1–90.Google Scholar
  65. Levine, J. M.& Stallcup, W. B.(1987) Plasticity of developing cerebellar cells in vitrostudied with antibodies against the NG2 antigen. Journal of Neuroscience 7, 2721–2731.Google Scholar
  66. Levine, J. M.& Card, J. P.(1987) Light and electron microscopic localization of a cell surface antigen (NG2) in the rat cerebellum: Association with smooth protoplasmic astrocytes. Journal of Neuroscience 7, 2711–2720.Google Scholar
  67. Levine, S. M.& Goldman, J. E.(1988) Spatial and temporal patterns of oligodendrocyte differentiation in rat cerebrum and cerebellum. J. Comp. Neurol. 277, 441–455.Google Scholar
  68. Levine, J. M.(1989) Neuronal influences on glial progenitor cell development. Neuron 3, 103–113.Google Scholar
  69. Levine, J. M., Stincone, F.& Lee, Y. S.(1993) Development and differentiation of glial precursor cells in the rat cerebellum. Glia 7, 307–321.Google Scholar
  70. Levine, J. M.(1994) Increased expression of the NG2 chondroitin-sulfate proteoglycan after brain injury. Journal of Neuroscience 14, 4716–4730.Google Scholar
  71. Levine, J. M.& Reynolds, R.(1999) Activation and proliferation of endogenous oligodendrocyte precursor cells during ethidium bromide-induced demyelination. Exp. Neurol. 160, 333–347.Google Scholar
  72. Levine, J. M., Reynolds, R.& Fawcett, J. W.(2001) The oligodendrocyte precursor cell in health and disease. Trends Neurosci. 24, 39–47.Google Scholar
  73. Levison, S. W.& Goldman, J. E.(1993) Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron 10, 201–212.Google Scholar
  74. Levison, S. W., Chuang, C., Abramson, B. J.& Goldman, J. E.(1993) The migrational patterns and developmental fates of glial precursors in the rat subventricular zone are temporally regulated. Development 119. 611–623.Google Scholar
  75. Levison, S. W., Young, G. M.& Goldman, J. E.(1999) Cycling cells in the adult rat neocortex preferentially generate oligodendroglia. J. Neurosci. Res. 57, 435–446.Google Scholar
  76. Lu, Q. R., Yuk, D., Alberta, J. A., Zhu, Z., Pawlitzky, I., Chan, J., McMahon, A. P., Stiles, C. D.& Rowitch, D. H.(2000) Sonic hedgehog–Regulated oligodendrocyte lineage genes encodingbHLHproteins in themammaliancentral nervous system. Neuron 25, 317–329.Google Scholar
  77. Lu, Q. R., Sun, T., Zhu, Z., Ma, N., Garcia, M., Stiles, C. D.& Rowitch, D. H.(2002) Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109, 75–86.Google Scholar
  78. Mallon, B. S., Shick, H. E., Kidd, G. J.& Macklin, W. B.(2002) Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical development. J. Neurosci. 22, 876–885.Google Scholar
  79. Marchionni, M. A., Goodearl, A. D., Chen, M. S., Bermingham-Mcdonogh, O., Kirk, C., Hendricks, M., Danehy, F., Misumi, D., Sudhalter, J., Kobayashi, K., et al.(1993) Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system. Nature 362, 312–318.Google Scholar
  80. Marmur, R., Kessler, J. A., Zhu, G., Gokhan, S.& Mehler, M. F.(1998) Differentiation of oligodendroglial progenitors derived from cortical multipotent cells requires extrinsic signals including activation of gp130/LIF beta receptors. Journal of Neuroscience 18, 9800–9811.Google Scholar
  81. Martin, S., Levine, A. K., Chen, Z. J., Ughrin, Y.& Levine, J. M.(2001) Deposition of the NG2 proteoglycan at nodes of Ranvier in the peripheral nervous system. J. Neurosci. 21, 8119–8128.Google Scholar
  82. Mason, J. L., Suzuki, K., Chaplin, D. D.& Matsushima, G. K.(2001) Interleukin-1beta promotes repair of the CNS. J. Neurosci. 21, 7046–7052.Google Scholar
  83. Mathias, K., Kirchloff, F., Seifert, G., Huttman, K., Matyash, M., Kettenmann, H.& Steinhauser, C.(2003) Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippo campus. J. Neurosci. 23(5), 1750–1758.Google Scholar
  84. McCarthy, G. F.& Leblond, C. P.(1988) 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.Google Scholar
  85. McTigue, D. M., Wei, P.& Stokes, B. T.(2001) Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J. Neurosci. 21, 3392–3400.Google Scholar
  86. Miller, R. H.(1996) Oligodendrocyte origins. Trends in the Neurosciences 19, 92–96.Google Scholar
  87. Mori, S.& Leblond, C. P.(1970) Electron microscopic idenfication of three classes of oligodendrocytes and a preliminary study of their proliferative activity in the corpus callosum of young rats. J. Comp. Neurol. 139, 1–30.Google Scholar
  88. Nait-Oumesmar, B., Decker, L., Lachapelle, F., Avellana-Adalid, V., Bachelin, C.& Van Evercooren, A. B.(1999) Progenitor cells of the adultmousesubventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur. J. Neurosci. 11, 4357–4366.Google Scholar
  89. Nakatsuji, Y.& Miller, R. H.(2001) Control of oligodendrocyte precursor proliferation mediated by densitydependent cell cycle protein expression. Dev. Neurosci. 23, 356–363.Google Scholar
  90. Nery, S., Wichterle, H.& Fishell, G.(2001) Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain. Development 128, 527–540.Google Scholar
  91. Niehaus, A., Stegmuller, J., Diers-Fenger, M.& Trotter, J.(1999) Cell-surface glycoprotein of oligodendrocyte progenitors involved in migration. Journal of Neuroscience 19, 4948–4961.Google Scholar
  92. Nishiyama, A., Dahlin, K. J., Prince, J. T., Johnstone, S. R.& Stallcup, W. B.(1991a) The primary structure of NG2, a novel membrane-spanning proteoglycan. Journal of Cell Biology 114, 359–371.Google Scholar
  93. Nishiyama, A., Dahlin, K. J.& Stallcup, W. B.(1991b) The expression of NG2 proteoglycan in the developing rat limb. Development 111, 933–944.Google Scholar
  94. Nishiyama, A., Lin, X.-H., Giese, N., Heldin, C.-H.& Stallcup, W. B.(1996a) Co-localization of NG2proteoglycan andPDGFa receptor onO2Aprogenitor cells in the developing rat brain. Journal of Neuroscience Research 43, 299–314.Google Scholar
  95. Nishiyama, A., Lin, X.-H., Giese, N., Heldin, C.-H.& Stallcup, W. B.(1996b) Interaction between NG2 proteoglycan and PDGF a receptor on O2A progenitor cells is required for optimal response to PDGF. Journal of Neuroscience Research 43, 315–330.Google Scholar
  96. Nishiyama, A., Yu, M., Drazba, J. A.& Tuohy, V. K.(1997) Normal and reactive NG2+glial cells are distinct from resting and activated microglia. Journal of Neuroscience Research 48, 299–312.Google Scholar
  97. Nishiyama, A., Chang, A.& Trapp, B. D.(1999) NG2+glial cells:Anovel glial cell population in the adult Identity, distribution, and development of polydendrocytes 453 brain. Journal of Neuropathology and Experimental Neurology 58, 1113–1124.Google Scholar
  98. Noble, M., Murray, K., Stroobant, P., Waterfield, M. D.& Riddle, P.(1988) Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature 333, 560–562.Google Scholar
  99. Olivier, C., Cobos, I., Perez Villegas, E. M., Spassky, N., Zalc, B., Martinez, S.& Thomas, J. L.(2001) Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo. Development 128, 1757–1769.Google Scholar
  100. Ong, W. Y.& Levine, J. M.(1999) A light and electron microscopic study of NG2 chondroitin sulfate proteoglycan-positive oligodendrocyte precursor cells in the normal and kainate-lesioned rat hippocampus. Neuroscience 92, 83–95.Google Scholar
  101. Ono, K., Yasui, Y., Rutishauser, U.& Miller, R. H.(1997) Focal ventricular origin and migration of oligodendrocyte precursors into the chick optic nerve. Neuron 19, 283–292.Google Scholar
  102. Orentas, D. M., Hayes, J. E., Dyer, K. L.& Miller, R. H.(1999) Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors. Development 126, 2419–2429.Google Scholar
  103. Orkand, R. K., Nicholls, J. G.& Kuffler, S. W.(1966) Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia. J. Neurophysiol. 29, 788–806.Google Scholar
  104. Oumesmar, B., Vignais, L.& Baron-Van Evercooren, A.(1997) Developmental expression of platelet-derived growth factor a-receptor in neurons and glial cells of the mouse CNS. Journal of Neuroscience 17, 125–139.Google Scholar
  105. Parnavelas, J.(1999) Glial cell lineages in the rat cerebral cortex. Exp. Neurol. 156, 418–429.Google Scholar
  106. Patneau, D. K., Wright, P. W., Winters, C., Mayer, M. L.& Gallo, V.(1994) Glial cells of the oligodendrocyte lineage express both kainateand AMPA-preferring subtypes of glutamate receptor. Neuron 12, 357–371.Google Scholar
  107. Perez Villegas, E. M., Olivier, C., Spassky, N., Poncet, C., Cochard, P., Zalc, B., Thomas, J. L.& Martinez, S.(1999) Early specification of oligodendrocytes in the chick embryonic brain. Dev. Biol. 216, 98–113.Google Scholar
  108. Perry, V. H.& Gordon, S.(1988) Macrophages and microglia in the nervous system. Trends in the Neurosciences 11, 273–277.Google Scholar
  109. Peters, A., Palay, S. L.& Def. Webster, H.(1991) The Fine Structure of the Nervous System, 3rd edition. New York: Oxford.Google Scholar
  110. Pfeiffer, S. E., Warrington, A. E.& Bansal, R.(1993) The oligodendrocyte and its many cellular processes. Trends in Cell Biology 3, 191–197.Google Scholar
  111. Pluschke, G., Vanek, M., Evans, A., Dittmar, T., Schmid, P., Itin, P., Filardo, E. J.& Reisfeld, R. A.(1996) Molecular cloning of a human melanomaassociated chondroitin sulfate proteoglycan. Proceedings of the National Academy of Sciences of the USA 93, 9710–9715.Google Scholar
  112. Poncet, C., Soula, C., Trousse, F., Kan, P., Hirsinger, E., Pourquie, O., Duprat, A. M.& Cochard, P.(1996) Induction of oligodendrocyte progenitors in the trunk neural tube by ventralizing signals: Effects of notochord and floor plate grafts, and of sonic hedgehog. Mech. Dev. 60, 13–32.Google Scholar
  113. Pringle, N. P., Mudhar, H. S., Collarini, E. J.& Richardson, W. D.(1992) 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.Google Scholar
  114. Pringle, N. P.& Richardson, W. D.(1993) 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.Google Scholar
  115. Pringle, N. P., Yu, W.-P., Guthrie, S., Roelink, H., Lumdsden, A., Peterson, A. C.& Richardson, W. D.(1996) Determination of neuroepithelial cell fate: Induction of the oligodendrocyte lineage by ventral midline cells and sonic hedgehog. Developmental Biology 177, 30–42.Google Scholar
  116. Privat, A.& Leblond, C. P.(1972) The subependymal layer and neighboring region in the brain of the young rat. J. Comp. Neurol. 146, 277–302.Google Scholar
  117. Raff, M. C., Miller, R. H.& Noble, M.(1983) A glial progenitor cell that develops in vitrointo an astrocyte or an oligodendrocyte depending on culture medium. Nature 303, 390–396.Google Scholar
  118. Raff, M. C., Lillien, L. E., Richardson, W. D., Burne, J. F.& Noble, M. D.(1988) Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature 333, 562–565.Google Scholar
  119. Ramon-Moliner, E.(1958) A study of neuroglia: The problem of transitional forms. J. Comp. Neurol. 110, 157–171.Google Scholar
  120. Ramon Y Cajal, S.(1913) Sobre un nuevo proceder de impregnacion de la neuroglia y sus resultados en los centros nerviosos del hombre y animales. Trab. Lab. Invest. Biol. Univ. Madrid 11, 219–237.Google Scholar
  121. Rao, M. S., Noble, M.& Mayer-Proschel, M.(1998) A tripotential glial precursor cell is present in the developing spinal cord. Proc. Natl. Acad. Sci. USA 95, 3996–4001.Google Scholar
  122. Redwine, J. M.& Armstrong, R. C.(1998) In vivoproliferation of oligodendrocyte progenitors expressing PDGFalphaR during early remyelination. J. Neurobiol. 37, 413–428.Google Scholar
  123. Reyners, H., Gianfelici De Reyners, E.& Maisin, J. R.(1982) The beta astrocyte: A newly recognized radiosensitive glial cell type in the cerebral cortex. Journal of Neurocytology 11, 967–983.Google Scholar
  124. Reyners, H., Gianfelici De Reyners, E., Regniers, L.& Maisin, J. R.(1986) A glial progenitor cell in the cerebral cortex of the adult rat. Journal of Neurocytology 15, 53–61.Google Scholar
  125. Reynolds, R.& Wilkin, G. P.(1988) Development of macroglial cells in rat cerebellum II. An in situ immunohistochemical study of oligodendroglial lineage from precursor to mature myelinating cell. Development 102, 409–425.Google Scholar
  126. Reynolds, R.& Wilkin, G. P.(1993) Cellular reaction to an acute demyelinating/remyelinating lesion of the rat brain stem: Localisation of GD3 ganglioside immunoreactivity. J. Neurosci. Res. 36, 405–422.Google Scholar
  127. Reynolds, R.& Hardy, R.(1997) Oligodendroglial progenitors labeled with the O4 antibody persist in the adult rat cerebral cortex in vivo. J. Neurosci. Res. 47, 455–470.Google Scholar
  128. Richardson, W. D., Pringle, N., Mosley, M. J., Westermark, B.& Dubois-Dalcq, M.(1988) A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell 53, 309–319.Google Scholar
  129. Richardson, W. D., Smith, H. K., Sun, T., Pringle, N. P., Hall, A.& Woodruff, R.(2000) Oligodendrocyte lineage and the motor neuron connection. Glia 29, 136–142.Google Scholar
  130. Richardson, W. D.(2001) Oligodendrocyte development. In Glial Cell Development(edited by Jessen, K. R.& Richardson, W. D.) pp. 21–54. Oxford University Press.Google Scholar
  131. Rio Hortega, P. D.(1928) Tercera aportacion al conocimiento morfologico e interpretacion funcional de la oligodendroglia. Mem. R. Soc. Esp. Hist. Nat. 14, 5–122.Google Scholar
  132. Roach, A., Takahashi, N., Pravtcheva, D., Ruddle, F.& Hood, L.(1985) Chromosomal mapping of mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell 42, 149–155.Google Scholar
  133. Rosenbluth, J.(1980) Central myelin in the mouse mutant shiverer. J. Comp. Neurol. 194, 639–648.Google Scholar
  134. Schneider, S., Bosse, F., D'urso, D., Muller, H., Sereda, M. W., Nave, K., Niehaus, A., Kempf, T., Schnolzer, M.& Trotter, J.(2001) The AN2 protein is a novel marker for the Schwann cell lineage expressed by immature and nonmyelinating Schwann cells. J. Neurosci. 21, 920–933.Google Scholar
  135. Schon, F.& Kelly, J. S.(1975) Selective uptake of (3H)beta-alanine by glia: Association with glial uptake system for GABA. Brain Res. 86, 243–257.Google Scholar
  136. Sedgwick, J. D., Schwender, S., Imrich, H., Dorries, R., Butcher, G. W.& Ter Meulen, V.(1991) Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc. Natl. Acad. Sci. USA 88, 7438–7442.Google Scholar
  137. Shi, J., Marinovich, A.& Barres, B. A.(1998) Purification and characterization of adult oligodendrocyte precursor cells from the rat optic nerve. Journal of Neuroscience 18, 4627–4636.Google Scholar
  138. Skoff, R. P.(1982) Increased proliferation of oligodendrocytes in the hypomyelinated mouse mutant-jimpy. Brain Res. 248, 19–31.Google Scholar
  139. Small, R. K., Riddle, P.& Noble, M.(1987) Evidence for migration of oligodendrocyte-type-2 astrocyte progenitor cells into the developing rat optic nerve. Nature 328, 155–157.Google Scholar
  140. Sontheimer, H., Trotter, J., Schachner, M.& Kettenmann, H.(1989) Channel expression correlates with differentiation stage during the development of oligodendrocytes from their precursor cells in culture. Neuron 2, 1135–1145.Google Scholar
  141. Sontheimer, H., Minturn, J. E., Black, J. A., Waxman, S. G.& Ransom, B. R.(1990) Specificity of cell-cell coupling in rat optic nerve astrocytes in vitro. Proc. Natl. Acad. Sci. USA 87, 9833–9837.Google Scholar
  142. Soula, C., Danesin, C., Kan, P., Grob, M., Poncet, C.& Cochard, P.(2001) Distinct sites of origin of oligodendrocytes and somatic motoneurons in the chick spinal cord: Oligodendrocytes arise fromNkx2.2-expressing progenitors by a Shh-dependent mechanism. Development 128, 1369–1379.Google Scholar
  143. Spassky, N., Goujet-Zalc, C., Parmantier, E., Olivier, C., Martinez, S., Ivanova, A., Ikenaka, K., Macklin, W., Cerruti, I., Zalc, B.& Thomas, J. L.(1998) Multiple restricted origin of oligodendrocytes. Journal of Neuroscience 18, 8331–8343.Google Scholar
  144. Spassky, N., Olivier, C., Perez-Villegas, E., Goujet-Zalc, C., Martinez, S., Thomas, J.& Zalc, B.(2000) Single or multiple oligodendroglial lineages: A controversy. Glia 29, 143–148.Google Scholar
  145. Spassky, N., Heydon, K., Mangatal, A., Jankovski, A., Olivier, C., Queraud-Lesaux, F., Goujet-Zalc, C., Thomas, J. L.& Zalc, B.(2001) Sonic hedgehog-dependent emergence of oligodendrocytes in the telencephalon: Evidence for a source of oligodendrocytes in the olfactory bulb that is independent of PDGFRalpha signaling. Development 128, 4993–5004.Google Scholar
  146. Stallcup, W. B., Beasley, L.& Levine, J.(1983) Cellsurface molecules that characterize different stages in the development of cerebellar interneurons. Cold Spring Harbor Symposia on Quantitative Biology XLVIII, 761–774.Google Scholar
  147. Stallcup, W. B.& Beasley, L.(1987) Bipotential glial precursor cells of the optic nerve express the NG2 proteoglycan. Journal of Neuroscience 7, 2737–2744.Google Scholar
  148. Stallcup, W. B., Dahlin, K.& Healy, P.(1990) Interaction of the NG2 chondroitin sulfate proteoglycan with type VI collagen. Journal of Cell Biology 111, 3177–3188.Google Scholar
  149. Steinhauser, C., Jabs, R.& Kettenmann, H.(1994) Properties of GABA and glutamate responses in identified glial cells of the mouse hippocampal slice. Hippocampus 4, 19–35.Google Scholar
  150. Takebayashi, H., Yoshida, S., Sugimori, M., Kosako, H., Kominami, R., Nakafuku, M.& Nabeshima, Y.(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. Mech. Dev. 99, 143–148.Google Scholar
  151. Tekki-Kessaris, N., Woodruff, R., Hall, A. C., Gaffield, W., Kimura, S., Stiles, C. D., Rowitch, D. H.& Richardson, W. D.(2001) Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. Development 128, 2545–2554.Google Scholar
  152. Trapp, B. D., Nishiyama, A., Cheng, D.& Macklin, W. B.(1997) Differentiation and death of premyelinating oligodendrocytes in developing rodent brain. Journal of Cell Biology 137, 459–468.Google Scholar
  153. Van Heyningen, P., Calver, A. R.& Richardson, W. D.(2001) Control of progenitor cell number by mitogen supply and demand. Curr. Biol. 11, 232–241.Google Scholar
  154. Walz, W.(2000) Controversy surrounding the existence of discrete functional classes of astrocytes in adult gray matter. Glia 31, 95–103.Google Scholar
  155. Warf, B. C., Fok-Seang, J.& Miller, R. H.(1991) Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord. Journal of Neuroscience 11, 2477–2488.Google Scholar
  156. Warrington, A. E.& Pfeiffer, S. E.(1992) Proliferation and differentiation of O4+oligodendrocytes in postnatal rat cerebellum: Analysis in tissue slices using anti-glycolipid antibodies. J. Neurosci. Res. 33, 338–353.Google Scholar
  157. Watanabe, M., Toyama, Y.& Nishiyama, A.(2002) Differentiation of proliferated NG2-positive glial progenitor cells in a remyelinating lesion. J. Neurosci. Res. 69(6), 826–836.Google Scholar
  158. Weiss, S., Dunne, C., Hewson, J., Wohl, C., Wheatley, M., Peterson, A. C.& Reynolds, B. A.(1996) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci. 16, 7599–7609.Google Scholar
  159. Williams, B. P., Read, J.& Price, J.(1991) The generation of neurons and oligodendrocytes from a common precursor cell. Neuron 7, 685–693.Google Scholar
  160. Williamson, A. V., Mellor, J. R., Grant, A. L.& Randall, A. D.(1998) Properties of GABAA receptors in cultured rat oligodendrocyte progenitor cells. Neuropharmacology 37, 859–873.Google Scholar
  161. Wolswijk, G.(1994)GD3+cells in the adult rat optic nerve are ramified microglia rather than O-2Aadult progenitor cells. Glia 10, 244–249.Google Scholar
  162. Wu, Q., Miller, R. H., Ransohoff, R. M., Robinson, S., Bu, J.& Nishiyama, A.(2000) Elevated levels of the chemokine GRO-1 correlate with elevated oligodendrocyte progenitor proliferation in the jimpy mutant. Journal of Neuroscience 20, 2609–2617.Google Scholar
  163. Yeh, H. J., Ruit, K. G., Wang, Y. X., Parks, W. C., Snider, W. D.& Deuel, T. F.(1991) PDGF A-chain gene is expressed by mammalian neurons during development and in maturity. Cell 64, 209–216.Google Scholar
  164. Yuan, X., Eisen, A. M., Mcbain, C. J.& Gallo, V.(1998) A role for glutamate and its receptors in the regulation of oligodendrocyte develoment in cerebellar tissue slices. Development 125, 2901–2914.Google Scholar
  165. Zerlin, M., Levison, S. W.& Goldman, J. E.(1995). Early stages of dispersion and differentiation of glial progenitors in the postnatal mammalian forebrain. J. Neurosci. 15, 7238–7249.Google Scholar
  166. Zhang, H.& Miller, R. H.(1996) Density-dependent feedback inhibition of oligodendrocyte precursor expansion. Journal of Neuroscience 16, 6886–6895.Google Scholar
  167. Zhou, Q., Wang, S.& Anderson, D. J.(2000) Identification of a novel family of oligodendrocyte lineagespecific basic helix-loop-helix transcription factors. Neuron 25, 331–343.Google Scholar
  168. Zhou, Q.& Anderson, D. J.(2002) ThebHLHtranscription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 109, 61–73.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Akiko Nishiyama
    • 1
  • Masahiko Watanabe
    • 1
  • Zhongshu Yang
    • 1
  • Jie Bu
    • 1
  1. 1.Department of Physiology and NeurobiologyUniversity of ConnecticutStorrsUSA

Personalised recommendations