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Molecular Neurobiology

, Volume 30, Issue 1, pp 49–76 | Cite as

Neural stem cells redefined

A FACS perspective
  • Dragan Maric
  • Jeffery L. Barker
Article

Abstract

Using the generally accepted ontogenetic definition, neural stem cells (NSCs) are characterized as undifferentiated cells originating from the neuroectoderm that have the capacity both to perpetually self-renew without differentiating and to generate multiple types of lineage-restricted progenitors (LRP). LRPs can themselves undergo limited self-renewal, then ultimately differentiate into highly specialized cells that compose the nervous system. However, this physiologically delimited definition of NSCs has been increasingly blurred in the current state of the field, as the great majority of studies have retrospectively inferred the existence of NSCs based on their deferred functional capability rather than prospectively identifying the actual cells that created the outcome. Further complicating the matter is the use of a wide variety of neuroepithelial or neurosphere preparations as a source of putative NSCs, without due consideration that these preparations are themselves composed of heterogeneous populations of both NSCs and LRPs. This article focuses on recent attempts using FACS strategies to prospectively isolate NSCs from different types of LRPs as they appear in vivo and reveals the contrasting differences among these populations at molecular, phenotypic, and functional levels. Thus, the strategies presented here provide a framework for more precise studies of NSC and LRP cell biology in the future.

Index Entries

central nervous system development cortex neural stem cells neural progenitors fluorescence-activated cell sorting cell fate 

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References

  1. 1.
    Gage F.H. (2000) Mammalian neural stem cells. Science 287, 1433–1438.PubMedCrossRefGoogle Scholar
  2. 2.
    Anderson D.J. (2001) Stem cells and pattern formation in the nervous system: the possible versus the actual. Neuron 30, 19–35.PubMedCrossRefGoogle Scholar
  3. 3.
    Temple S. (2001) Stem cell plasticity—building the brain of our dreams. Nat. Rev. Neurosci. 2, 513–520.PubMedCrossRefGoogle Scholar
  4. 4.
    Temple S. (2001) The development of neural stem cells. Nature 414, 112–117.PubMedCrossRefGoogle Scholar
  5. 5.
    Vaccarino F.M., Ganat Y., Zhang Y., and Zheng W. (2001) Stem cells in neurodevelopment and plasticity. Neuropsychopharmacology 25, 805–815.PubMedCrossRefGoogle Scholar
  6. 6.
    Vescovi A.L., Galli R., and Gritti A. (2001) The neural stem cells and their transdifferentiation capacity. Biomed. Pharmacother. 55, 201–205.PubMedCrossRefGoogle Scholar
  7. 7.
    Weissman I.L., Anderson D.J., and Gage F. (2001) Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu. Rev. Cell. Dev. Biol. 17, 387–403.PubMedCrossRefGoogle Scholar
  8. 8.
    Gottlieb D.I. (2002) Large-scale sources of neural stem cells. Annu. Rev. Neurosci. 25, 381–407.PubMedCrossRefGoogle Scholar
  9. 9.
    Gritti A., Vescovi A.L., and Galli R. (2002) Adult neural stem cells: plasticity and developmental potential. J. Physiol. 96, 81–90.Google Scholar
  10. 10.
    Kennea N.L. and Mehmet H. (2002) Neural stem cells. J. Pathol. 197, 536–550.PubMedCrossRefGoogle Scholar
  11. 11.
    Kruger G.M. and Morrison S.J. (2002) Brain repair by endogenous progenitors. Cell 110, 399–402.PubMedCrossRefGoogle Scholar
  12. 12.
    Panchision D.M. and McKay R.D. (2002) The control of neural stem cells by morphogenic signals. Curr. Opin. Genet. Dev. 12, 478–487.PubMedCrossRefGoogle Scholar
  13. 13.
    Tsai R.Y., Kittappa R., and McKay R.D. (2002) Plasticity, niches, and the use of stem cells. Dev. Cell. 2, 707–712.PubMedCrossRefGoogle Scholar
  14. 14.
    Cai J. and Rao M.S. (2002) Stem cell and precursor cell therapy. Neuromolecular Med. 2, 233–249.PubMedCrossRefGoogle Scholar
  15. 15.
    Galli R., Gritti A., Bonfanti L., and Vescovi A.L. (2003) Neural stem cells: an overview. Circ. Res. 92, 598–608.PubMedCrossRefGoogle Scholar
  16. 16.
    Limke T.L. and Rao M.S. (2002) Neural stem cells in aging and disease. J. Cell. Mol. Med. 6, 475–496.PubMedCrossRefGoogle Scholar
  17. 17.
    Pevny L. and Rao M.S. (2003) The stem-cell menagerie. Trends Neurosci. 351–359.Google Scholar
  18. 18.
    Arsenijevic Y. (2003) Mammalian neural stem-cell renewal: nature versus nurture. Mol. Neurobiol. 27, 73–98.PubMedCrossRefGoogle Scholar
  19. 19.
    Seaberg R.M. and van der Kooy D. (2003) Stem and progenitor cells: the premature desertion of rigorous definitions. Trends Neurosci. 26, 125–131.PubMedCrossRefGoogle Scholar
  20. 20.
    Johansson C.B. (2003) Mechanisms of stem cells in the central nervous system. J. Cell. Physiol. 196, 409–418.PubMedCrossRefGoogle Scholar
  21. 21.
    Bjornson C.R., Rietze R.L., Reynolds B.A., Magli M.C., and Vescovi A.L. (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283, 534–537.PubMedCrossRefGoogle Scholar
  22. 22.
    Galli R., Borello U., Gritti A., Minasi M.G., Bjornson C., Coletta M., et al. (2000) Skeletal myogenic potential of human and mouse neural stem cells. Nat. Neurosci. 3, 986–991.PubMedCrossRefGoogle Scholar
  23. 23.
    Anderson D.J., Gage F.H., and Weissman I.L. (2001) Can stem cells cross lineage boundaries? Nat. Med. 7, 393–395.PubMedCrossRefGoogle Scholar
  24. 24.
    Liu Y. and Rao M.S. (2003) Transdifferentiation—fact or artifact. J. Cell. Biochem. 88, 29–40.PubMedCrossRefGoogle Scholar
  25. 25.
    Tropepe V., Sibilia M., Ciruna B.G., Rossant J., Wagner E.F., and van der Kooy D. (1999) Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev. Biol. 208, 166–188.PubMedCrossRefGoogle Scholar
  26. 26.
    Martens D.J., Tropepe V., and van Der Kooy D. (2000) Separate proliferation kinetics of fibroblast growth factor-responsive and epidermal growth factor-responsive neural stem cells within the embryonic forebrain germinal zone. J. Neurosci. 20, 1085–1095.PubMedGoogle Scholar
  27. 27.
    Kallos M.S., Sen A., and Behie L.A. (2003) Large-scale expansion of mammalian neural stem cells: a review. Med. Biol. Eng. Comput. 41, 271–282.PubMedCrossRefGoogle Scholar
  28. 28.
    Davis A.A. and Temple S. (1994) A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature 372, 263–266.PubMedCrossRefGoogle Scholar
  29. 29.
    Reynolds B.A. and Weiss S. (1996) Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev. Biol. 175, 1–13.PubMedCrossRefGoogle Scholar
  30. 30.
    Suslov O.N., Kukekov V.G., Ignatova T.N., and Steindler D.A. (2002) Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc. Natl. Acad. Sci. USA 99, 14,506–14,511.CrossRefGoogle Scholar
  31. 31.
    Kalyani A.J., Mujtaba T., and Rao M.S. (1999) Expression of EGF receptor and FGF receptor isoforms during neuroepithelial stem cell differentiation. J. Neurobiol. 38, 207–224.PubMedCrossRefGoogle Scholar
  32. 32.
    Qian X., Davis A.A., Goderie S.K., and Temple S. (1997) FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells. Neuron 18, 81–93.PubMedCrossRefGoogle Scholar
  33. 33.
    Morrison S.J., White P.M., Zock C., and Anderson D.J. (1999) Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells. Cell 96, 737–749.PubMedCrossRefGoogle Scholar
  34. 34.
    White P.M., Morrison S.J., Orimoto K., Kubu C.J., Verdi J.M., and Anderson D.J. (2001) Neural crest stem cells undergo cell-intrinsic developmental changes in sensitivity to instructive differentiation signals. Neuron 29, 57–71.PubMedCrossRefGoogle Scholar
  35. 35.
    Bixby S., Kruger G.M., Mosher J.T., Joseph N. M., and Morrison S.J. (2002) Cell-intrinsic differences between stem cells from different regions of the peripheral nervous systems regulate the generation of neural diversity. Neuron 35, 643–656.PubMedCrossRefGoogle Scholar
  36. 36.
    Uchida N., Buck D.W., He D., Reitsma M.J., Masek M., Phan T.V., et al. (2000) Direct isolation of human central nervous system stem cells. Proc. Natl. Acad. Sci. USA 97, 14,720–14,725.CrossRefGoogle Scholar
  37. 37.
    Rietze R.L., Valcanis H., Brooker G.F., Thomas T., Voss A.K., and Bartlett P.F. (2001) Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 412, 736–739.PubMedCrossRefGoogle Scholar
  38. 38.
    Cai J., Wu Y., Mirua T., Pierce J.L., Lucero M.T., Albertine K.H., et al. (2002) Properties of a fetal multipotent neural stem cell (NEP cell). Dev. Biol. 251, 221–240.PubMedCrossRefGoogle Scholar
  39. 39.
    Leemhuis T., Yoder M.C., Grigsby S., Aguero B., Eder P., and Srour E.F. (1996) Isolation of primitive human bone marrow hematopoietic progenitor cells using Hoechst 33342 and Rhodamine 123. Exp. Hematol. 24, 1215–1224.PubMedGoogle Scholar
  40. 40.
    Radley J.M., Ellis S., Palatsides M., Williams B., and Bertoncello I. (1999) Ultrastructure of primitive hematopoietic stem cells isolated using probes of functional status. Exp. Hematol. 27, 365–369.PubMedCrossRefGoogle Scholar
  41. 41.
    Kawaguchi A., Miyata T., Sawamoto K., Takashita N., Murayama A., Akamatsu W., et al. (2001) Nestin-EGFP transgenic mice: visualization of the self-renewal and multipotency of CNS stem cells. Mol. Cell. Neurosci. 17, 259–273.PubMedCrossRefGoogle Scholar
  42. 42.
    Hilbig R., Rosner H., and Rahmann H. (1981) Phylogenetic recapitulation of brain ganglioside composition during ontogenetic development. Comp. Biochem. Physiol. 68, 301–305.CrossRefGoogle Scholar
  43. 43.
    Hilbig R., Rosner H., Merz G., Segler-Stahl K., and Rahmann H. (1982) Developmental profiles of gangliosides in mouse and rat cerebral cortex. Wilhelm Roux’s Archives 191, 281–284.CrossRefGoogle Scholar
  44. 44.
    Yu R.K., Macala L.J., Taki T., Weinfield H.M., and Yu F.S. (1988) Developmental changes in ganglioside composition and synthesis in embryonic rat brain. J. Neurochem. 50, 1825–1829.PubMedCrossRefGoogle Scholar
  45. 45.
    Rogers T.B. and Snyder S.H. (1981) High affinity binding of tetanus toxin to mammalian brain membranes. J. Biol. Chem. 256, 2402–2407.PubMedGoogle Scholar
  46. 46.
    Fishman P.H. (1982) Role of membrane gangliosides in the binding and action of bacterial toxins. J. Membr. Biol. 69, 85–97.PubMedCrossRefGoogle Scholar
  47. 47.
    Halpern J.L. and Loftus A. (1993) Characterization of the receptor-binding domain of tetanus toxin. J. Biol. Chem. 268, 11,188–11,192.Google Scholar
  48. 48.
    Shapiro R.E., Specht C.D., Collins B.E., Woods A.S., Cotter R.J., and Schnaar R.L. (1997) Identification of a ganglioside recognition domain of tetanus toxin using a novel ganglioside photoaffinity ligand. J. Biol. Chem. 272, 30,380–30,386.CrossRefGoogle Scholar
  49. 49.
    Kundu S.K., Pleatman M.A., Redwine W.A., Boyd A.E., and Marcus D.M. (1983) Binding of monoclonal antibody A2B5 to gangliosides. Biochem. Biophys. Res. Commun. 116, 836–842.PubMedCrossRefGoogle Scholar
  50. 50.
    Kasai N. and Yu R.K. (1983) The monoclonal antibody A2B5 is specific to ganglioside GQ1c. Brain Res. 277, 155–158.PubMedCrossRefGoogle Scholar
  51. 51.
    Schwarz A. and Futerman A.H. (1996) The localization of gangliosides in neurons of the central nervous system: the use of anti-ganglioside antibodies. Biochem. Biophys. Acta 1286, 247–267.PubMedGoogle Scholar
  52. 52.
    Farrer R.G. and Quarles R.H. (1999) GT3 and its O-acetylated derivative are the principal A2B5-reactive gangliosides in cultured O2A lineage cells and are down-regulated among with O-acetyl GD3 during differentiation to oligodendrocytes. J. Neurosci. Res. 57, 371–380.PubMedCrossRefGoogle Scholar
  53. 53.
    Raff M.C., Fields K.L., Hakomori S.I., Mirsky R., Pruss R.M., and Winter J. (1979) Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture. Brain Res. 174, 283–308.PubMedCrossRefGoogle Scholar
  54. 54.
    Koulakoff A., Bizzini B., and Berwald-Netter Y. (1983) Neuronal acquisition of tetanus toxin binding sites: relationship with the last mitotic cycle. Dev. Biol. 100, 350–357.PubMedCrossRefGoogle Scholar
  55. 55.
    Raff M.C., Abney E.R., Cohen J., Lindsay R., and Noble M. (1983) Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides, and growth characteristics. J. Neurosci. 3, 1289–1300.PubMedGoogle Scholar
  56. 56.
    Abney E.R., Williams B.P., and Raff M.C. (1983) Tracing the development of oligodendrocytes from precursor cells using monoclonal antibodies, fluorescence-activated cell sorting, and cell culture. Dev. Biol. 100, 166–171.PubMedCrossRefGoogle Scholar
  57. 57.
    Behar T., McMorris F.A., Novotny E.A., Barker J.L., and Dubois-Dalcq M. (1988) Growth and differentiation properties of O-2A progenitors purified from rat cerebral hemispheres. J. Neurosci. Res. 21, 168–180.PubMedCrossRefGoogle Scholar
  58. 58.
    Bottenstein J.E., Hunter S.F., and Seidel M. (1998) CNS neuronal cell line-derived factors regulate gliogenesis in neonatal rat brain cultures. J. Neurosci. Res. 20, 291–303.CrossRefGoogle Scholar
  59. 59.
    Scolding N.J., Rayner P.J., and Compston D.A. (1999) Identification of A2B5-positive putative oligodendrocyte progenitor cells and A2B5-positive astrocytes in adult human white matter. Neuroscience 89, 1–4.PubMedCrossRefGoogle Scholar
  60. 60.
    Shindler K.S. and Roth K.A. (1996) Cholera toxin binds to differentiating neurons in the developing murine basal ganglia. Brain Res. Dev. Brain. Res. 92, 199–210.PubMedCrossRefGoogle Scholar
  61. 61.
    Blum A.S. and Barnstable C.J. (1987) O-acetylation of a cell-surface carbohydrate creates discrete molecular patterns during neural development. Proc. Natl. Acad. Sci. USA 84, 8716–8720.PubMedCrossRefGoogle Scholar
  62. 62.
    Mendez-Otero R., Schlosshauer B., Barnstable C.J., and Constantine-Paton M. (1988) A developmentally regulated antigen associated with neural cell and process migration. J. Neurosci. 8, 564–579.PubMedGoogle Scholar
  63. 63.
    Santiago M.F., Berredo-Pinho M., Costa M.R., Gandra M., Cavalcante L.A., et al. (2001) Expression and function of ganglioside 9-Oacetyl GD3 in postmitotic granule cell development. Mol. Cell. Neurosci. 17, 488–499.PubMedCrossRefGoogle Scholar
  64. 64.
    Miyakoshi L.M., Mendez-Otero R., and Hedin-Pereira C. (2001) The 9-O-acetyl GD3 gangliosides are expressed by migrating chains of subventricular zone neurons in vitro. Braz. J. Med. Biol. Res. 34, 669–673.PubMedCrossRefGoogle Scholar
  65. 65.
    Maric D., Maric I., and Barker J.L. (1999) Flow cytometric strategies to study CNS development. In Neuromethods, vol. 33, (Boulton A.A., and Baker G.B., eds.), Harmana Press, Totowa, NJ, pp. 287–318.Google Scholar
  66. 66.
    Maric D., Maric I., Chang Y.H., and Barker J.L. (2000) Stereotypic physiological properties emerge during early neuronal and glial lineage development in the embryonic rat neocortex. Cerebral Cortex 10, 729–747.PubMedCrossRefGoogle Scholar
  67. 67.
    Maric D., Maric I., Chang Y.H., and Barker J.L. (2003) Prospective cell sorting of embryonic rat neural stem cells and neuronal and glial progenitors reveals selective effects of basic fibroblast growth factor and epidermal growth factor on self-renewal and differentiation. J. Neurosci. 23, 240–251.PubMedGoogle Scholar
  68. 68.
    Koopman G., Reutelingsperger C.P., Kuijten G.A., Keehnen R.M., Pals S.T., and van Oers M.H. (1994) Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84, 1415–1420.PubMedGoogle Scholar
  69. 69.
    Martin S.J., Reutelingsperger C.P., McGahon A.J., Rader J.A., van Schie R.C., LaFace D.M., et al. (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med. 182, 1545–1556.PubMedCrossRefGoogle Scholar
  70. 70.
    Maric D., Maric I., Ma W., Lahojuji F., Somogyi R., Wen X., et al. (1997) Anatomical gradients in proliferation and differentiation of embryoni.c rat CNS accessed by buoyant density fractionation: alpha 3, beta 3 and gamma 2 GABAA receptor subunit co-expression by post-mitotic neocortical neurons correlates directly with cell buoyancy. Eur. J. Neurosci. 9, 507–522.PubMedCrossRefGoogle Scholar
  71. 71.
    Maric D., Maric I., and Barker J.L. (1998) Buoyant density gradient fractionation and flow cytometric analysis of embryonic rat cortical neurons and progenitor cells. Methods 16, 247–259.PubMedCrossRefGoogle Scholar
  72. 72.
    Geschwind D.H., Ou J., Easterday M.C., Dougherty J.D., Jackson R.L., Chen Z., et al. (2001) A genetic analysis of neural progenitor differentiation. Neuron 29, 325–339.PubMedCrossRefGoogle Scholar
  73. 73.
    Terskikh A.V., Easterday M.C., Li L., Hood L., Kornblum H.I., Geschwind D.H., et al. (2001) From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc. Natl. Acad. Sci. USA 98, 7934–7939.PubMedCrossRefGoogle Scholar
  74. 74.
    Wright L.S., Li J., Caldwell M.A., Wallace K., Johnson J.A., and Svendsen C.N. (2003) Gene expression in human neural stem cells: effects of leukemia inhibitory factor. J. Neurochem. 86, 179–195.PubMedCrossRefGoogle Scholar
  75. 75.
    Malatesta P., Hartfuss E., and Gotz M. (2000) Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127, 5253–5263.PubMedGoogle Scholar
  76. 76.
    Tamamaki N., Nakamura K., Okamoto K., and Kaneko T. (2001) Radial glia is a progenitor of neocortical neurons in the developing cerebral cortex. Neurosci. Res. 41, 51–60.PubMedCrossRefGoogle Scholar
  77. 77.
    Noctor S.C., Flint A.C., Weissman T.A., Dammerman R.S., and Kriegstein A.R. (2001) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–720.PubMedCrossRefGoogle Scholar
  78. 78.
    Noctor S.C., Flint A.C., Weissman T.A., Wong W.S., Clinton B.K., and Kriegstein A.R. (2002) Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia. J. Neurosci. 22, 3161–3173.PubMedGoogle Scholar
  79. 79.
    Luo Y., Cai J., Liu Y., Xue H., Chrest F.J., Wersto R.P., et al. (2002) Microarray analysis of selected genes in neural stem and progenitor cells. J. Neurochem. 83, 1481–1497.PubMedCrossRefGoogle Scholar
  80. 80.
    LoTurco J.J., Owens D.F., Heath M.J., Davis M.B., and Kriegstein A.R. (1995) GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis. Neuron 15, 1287–1298.PubMedCrossRefGoogle Scholar
  81. 81.
    Wang C., Pralong W.F., Schulz M.F., Rougon G., Aubry J.M., Pagliusi S., et al. (1996) 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.PubMedCrossRefGoogle Scholar
  82. 82.
    Antonopoulos J., Pappas I.S., and Parnavelas J.G. (1997) Activation of the GABAA receptor inhibits the proliferative effects of bFGF in cortical progenitor cells. Eur. J. Neurosci. 9, 291–298.PubMedCrossRefGoogle Scholar
  83. 83.
    Sah D.W., Ray J., and Gage F.H. (1997) Regulation of voltage- and ligand-gated currents in rat hippocampal progenitor cells in vitro. J. Neurobiol. 32, 95–110.PubMedCrossRefGoogle Scholar
  84. 84.
    Cameron H.A., Hazel T.G., and McKay R.D. (1998) Regulation of neurogenesis by growth factors and neurotransmitters. J. Neurobiol. 36, 287–306.PubMedCrossRefGoogle Scholar
  85. 85.
    Lauder J.M., Liu J., Devaud L., and Morrow A.L. (1998) GABA as a trophic factor for developing monoamine neurons. Perspect. Dev. Neurobiol. 5, 247–259.PubMedGoogle Scholar
  86. 86.
    Weiss E.R., Maness P., and Lauder J.M. (1998) Why do neurotransmitters act like growth factors? Perspect. Dev. Neurobiol. 5, 323–335.PubMedGoogle Scholar
  87. 87.
    Ma W., Liu Q.Y., Maric D., Sathanoori R., Chang Y.H., and Barker J.L. (1998) Basic FGF-responsive telencephalic precursor cells express functional GABA(A) receptor/Cl channels in vitro. J. Neurobiol. 35, 277–286.PubMedCrossRefGoogle Scholar
  88. 88.
    Nguyen L., Rigo J.M., Rocher V., Belachew S., Malgrange B., Rogister B., et al. (2001) Neurotransmitters as early signals for central nervous system development. Cell Tissue Res. 305, 187–202.PubMedCrossRefGoogle Scholar
  89. 89.
    Kalyani A.J., Piper D., Mujtaba T., Lucero M.T., and Rao M.S. (1998) Spinal cord neuronal precursors generate multiple neuronal phenotypes in culture. J. Neurosci. 18, 7856–7868.PubMedGoogle Scholar
  90. 90.
    Mujtaba T., Piper D.R., Kalyani A., Groves A.K., Lucero M.T., and Rao M.S. (1999) Lineage-restricted neural precursors can be isolated from both the mouse neural tube and cultured ES cells. Dev. Biol. 214, 113–127.PubMedCrossRefGoogle Scholar
  91. 91.
    Piper D.R., Mujtaba T., Keyoung H., Roy N.S., Goldman S.A., Rao M.S., et al. (2001) Identification and characterization of neuronal precursors and their progeny from human fetal tissue. J. Neurosci. Res. 66, 356–368.PubMedCrossRefGoogle Scholar
  92. 92.
    Piper D.R., Mujtaba T., Rao M.S., and Lucero M.T. (2000) Immunocytochemical and physiological characterization of a population of cultured human neural precursors. J. Neurophysiol. 84, 534–548.PubMedGoogle Scholar
  93. 93.
    Ma W., Maric D., Li B.S., Hu Q., Andreadis J.D., Grant G.M., et al. (2000) Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and map kinase phosphorylation. Eur. J. Neurosci. 12, 1–4.CrossRefGoogle Scholar
  94. 94.
    Schambra U.B., Sulik K.K., Petrusz P., and Lauder J.M. (1989) Ontogeny of cholinergic neurons in the mouse forebrain. J. Comp. Neurol. 288, 101–122.PubMedCrossRefGoogle Scholar
  95. 95.
    Maric D., Maric I., and Barker J.L. (2000) Developmental changes in cell calcium homeostasis during neurogenesis of the embryonic rat cerebral cortex. Cerebral Cortex 10, 561–573.PubMedCrossRefGoogle Scholar
  96. 96.
    Maric D., Maric I., and Barker J.L. (2000) Dual videomicroscopic imaging of membrane potential and cytosolic calcium of immunoidentified embryonic rat cortical cells. Methods 21, 335–347.PubMedCrossRefGoogle Scholar
  97. 97.
    Maric D., Liu Q.Y., Maric I., Chaudry S., Chang Y.H., Smith S.V., et al. (2001) GABA expression dominates neuronal lineage progression in the embryonic rat neocortex and facilitates neurite outgrowth via GABAA autoreceptor/Cl channels. J. Neurosci. 21, 2343–2360.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  1. 1.Laboratory of Neurophysiology, National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesda

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