Skip to main content
SpringerLink
Log in

Defining Neural Stem Cells and Their Role in Normal Development of the Nervous System

  • Chapter
Neural Development and Stem Cells

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Stem cells are key players in the development and maintenance of specific mammalian tissues, and their presence has been long established in blood, skin, and intestine. The discovery of stem cells in the central and peripheral nervous systems (CNS and PNS) is a relatively recent event. First, continued neurogenesis (neuron generation) in the adult pointed to a long-lived progenitor cell (1). Isolation of stem-like cells from the embryonic CNS, including basal forebrain (2,3), cerebral cortex (4), hippocampus (5), spinal cord (6), and the PNS (7) as well as evidence for multipotent, stem-like progenitors in vivo (8–10) indicated that they are important components of the developing nervous system (Fig. 1). Much excitement surrounded the isolation of adult stem cells from known neurogenic (neuron-generating) zones (the subventricular zone and hippocampal dentate gyrus) in rat, primate, and human (reviewed in ref. 11). More recent evidence for continued presence of stem cells in areas not previously considered to be neurogenic, such as the spinal cord (12,13) and neocortex (14,15), suggests that stem cells may be a more widespread feature of the adult nervous system than previously imagined (Fig. 1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 149.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Altman, J. (1970) in Developmental Neurobiology (Himwich, W. A., ed.), Charles C Thomas, Springfield, IL, pp. 197–237.

    Google Scholar 

  2. Temple, S. (1989) Division and differentiation of isolated CNS blast cells in microcul-ture. Nature 340, 471–473.

    PubMed  CAS  Google Scholar 

  3. Reynolds, B. A., Tetzlaff, W., and Weiss, S. (1992) A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J. Neurosci. 12, 4565–4574.

    PubMed  CAS  Google Scholar 

  4. Davis, A. A. and Temple, S. (1994) A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature 372, 263–266.

    PubMed  CAS  Google Scholar 

  5. Johe, K. K., Hazel, T. G., Muller, T., Dugich-Djordjevic, M. M., and McKay, R. D. (1996) Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. Genes Dev. 10, 3129–3140.

    PubMed  CAS  Google Scholar 

  6. Kalyani, A., Hobson, K., and Rao, M. S. (1997) Neuroepithelial stem cells from the embryonic spinal cord: isolation, characterization, and clonal analysis. Dev. Biol. 186, 202–223.

    PubMed  CAS  Google Scholar 

  7. Stemple, D. L. and Anderson, D. J. (1992) Isolation of a stem cell for neurons and glia from the mammalian neural crest. Cell 71, 973–985.

    PubMed  CAS  Google Scholar 

  8. Walsh, C. and Cepko, C. L. (1993) Clonal dispersion in proliferative layers of developing cerebral cortex. Nature 362, 632–635.

    PubMed  CAS  Google Scholar 

  9. Leber, S. M. and Sanes, J. R. (1991) Lineage analysis with a recombinant retrovirus: application to chick spinal motor neurons. Adv. Neurol. 56, 27–36.

    PubMed  CAS  Google Scholar 

  10. Sanes, J. R. (1989) Analysing cell lineage with a recombinant retrovirus. Trends Neurosci. 12, 21–28.

    PubMed  CAS  Google Scholar 

  11. Temple, S. (1999) CNS development: the obscure origins of adult stem cells. Curr. Biol. 9, R397–R399.

    PubMed  CAS  Google Scholar 

  12. Weiss, S., Dunne, C., Hewson, J., et al. (1996) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci. 16, 7599–7609.

    PubMed  CAS  Google Scholar 

  13. Shihabuddin, L. S., Ray, J., and Gage, F. H. (1997) FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord. Exp. Neurol. 148, 577–586.

    PubMed  CAS  Google Scholar 

  14. Gould, E., Reeves, A. J., Graziano, M. S., and Gross, C. G. (1999) Neurogenesis in the neocortex of adult primates. Science 286, 548–552.

    PubMed  CAS  Google Scholar 

  15. Marmur, R., Mabie, P. C., Gokhan, S., Song, Q., Kessler, J. A., and Mehler, M. F. (1998) Isolation and developmental characterization of cerebral cortical multipotent progenitors. Dev. Biol. 204, 577–591.

    PubMed  CAS  Google Scholar 

  16. Morrison, S. J., Shah, N. M., and Anderson, D. J. (1997) Regulatory mechanisms in stem cell biology. Cell 88, 287–298.

    PubMed  CAS  Google Scholar 

  17. Morrison, S. J., Uchida, N., and Weissman, I. L. (1995) The biology of hematopoietic stem cells. Annu. Rev. Cell Dev. Biol. 11, 35–71.

    PubMed  CAS  Google Scholar 

  18. Okabe, S., Forsberg-Nilsson, K., Spiro, A. C., Segal, M., and McKay, R. D. (1996) Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro. Mech. Dev. 59, 89–102.

    PubMed  CAS  Google Scholar 

  19. Dinsmore, J., Ratliff, J., Deacon, T., et al. (1996) Embryonic stem cells differentiated in vitro as a novel source of cells for transplantation. Cell Transplant. 5, 131–143.

    PubMed  CAS  Google Scholar 

  20. Renoncourt, Y., Carroll, P., Filippi, P., Arce, V., and Alonso, S. (1998) Neurons derived in vitro from ES cells express homeoproteins characteristic of motoneurons and interneurons. Mech. Dev. 79, 185–197.

    PubMed  CAS  Google Scholar 

  21. Brustle, O., Jones, K. N., Learish, R. D., et al. (1999) Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285, 754–756.

    PubMed  CAS  Google Scholar 

  22. 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.

    PubMed  CAS  Google Scholar 

  23. Mujtaba, T., Mayer-Proschel, M., and Rao, M. S. (1998) A common neural progenitor for the CNS and PNS. Dev. Biol. 200, 1–15.

    PubMed  CAS  Google Scholar 

  24. Temple, S. and Alvarez-Buylla, A. (1999) Stem cells in the adult mammalian central nervous system. Curr. Opin. Neurobiol. 9, 135–141.

    PubMed  CAS  Google Scholar 

  25. Gage, F. H., Kempermann, G., Palmer, T. D., Peterson, D. A., and Ray, J. (1998) Multipotent progenitor cells in the adult dentate gyrus. J. Neurobiol. 36, 249–266.

    PubMed  CAS  Google Scholar 

  26. Gage, F. H., Coates, P. W., Palmer, T. D., et al. (1995) Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc. Natl. Acad. Sci. USA 92, 11879–11883.

    PubMed  CAS  Google Scholar 

  27. Cameron, H. A. and McKay, R. (1998) Stem cells and neurogenesis in the adult brain. Curr. Opin. Neurobiol. 8, 677–680.

    PubMed  CAS  Google Scholar 

  28. Kuhn, H. G. and Svendsen, C. N. (1999) Origins, functions, and potential of adult neural stem cells. Bioessays 21, 625–630.

    PubMed  CAS  Google Scholar 

  29. Rao, M. S. (1999) Multipotent and restricted precursors in the central nervous system. Anat. Rec. 257, 137–148.

    PubMed  CAS  Google Scholar 

  30. 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.

    PubMed  CAS  Google Scholar 

  31. Anderson, D. J. (1997) Cellular and molecular biology of neural crest cell lineage determination. Trends Genet. 13, 276–280.

    PubMed  CAS  Google Scholar 

  32. Anderson, D. J., Groves, A., Lo, L., et al. (1997) Cell lineage determination and the control of neuronal identity in the neural crest. Cold Spring Harb. Symp. Quant. Biol. 62, 493–504.

    PubMed  CAS  Google Scholar 

  33. LaBonne, C. and Bronner-Fraser, M. (1998) Induction and patterning of the neural crest, a stem cell-like precursor population. J. Neurobiol. 36, 175–189.

    PubMed  CAS  Google Scholar 

  34. Gaiano, N. and Fishell, G. (1998) Transplantation as a tool to study progenitors within the vertebrate nervous system. J. Neurobiol. 36, 152–161.

    PubMed  CAS  Google Scholar 

  35. Na, E., McCarthy, M., Neyt, C., Lai, E., and Fishell, G. (1998) Telencephalic progenitors maintain anteroposterior identities cell autonomously. Curr. Biol. 8, 987–990.

    PubMed  CAS  Google Scholar 

  36. Takahashi, M., Palmer, T. D., Takahashi, J., and Gage, F. H. (1998) Widespread integration and survival of adult-derived neural progenitor cells in the developing optic retina. Mol. Cell Neurosci. 12, 340–348.

    PubMed  CAS  Google Scholar 

  37. Campbell, K. and Bjorklund, A. (1995) Neurotransmitter-related gene expression in intrastriatal striatal transplants. III. Regulation by host cortical and dopaminergic afferents. Brain Res. Mol. Brain Res. 29, 263–272.

    PubMed  CAS  Google Scholar 

  38. Frantz, G. D. and McConnell, S. K. (1996) Restriction of late cerebral cortical progenitors to an upper-layer fate. Neuron 17, 55–61.

    PubMed  CAS  Google Scholar 

  39. Olsson, M., Campbell, K., and Turnbull, D. H. (1997) Specification of mouse telencephalic and mid-hindbrain progenitors following heterotopic ultrasound-guided embryonic transplantation. Neuron 19, 761–772.

    PubMed  CAS  Google Scholar 

  40. Suhonen, J. O., Peterson, D. A., Ray, J., and Gage, F. H. (1996) Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature 383, 624–627.

    PubMed  CAS  Google Scholar 

  41. Herrera, D. G., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (1999) Adult-derived neural precursors transplanted into multiple regions in the adult brain. Ann. Neurol. 46, 867–877.

    PubMed  CAS  Google Scholar 

  42. Quinn, S. M., Walters, W. M., Vescovi, A. L., and Whittemore, S. R. (1999) Lineage restriction of neuroepithelial precursor cells from fetal human spinal cord. J. Neurosci. Res. 57, 590–602.

    PubMed  CAS  Google Scholar 

  43. 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.

    PubMed  CAS  Google Scholar 

  44. Clarke, D. L., Johansson, C. B., Wilbertz, J., et al. (2000) Generalized potential of adult neural stem cells. Science 288, 1660–1663.

    PubMed  CAS  Google Scholar 

  45. Uchida, N., Buck, D. W., He, D., et al. (2000) Direct isolation of human central nervous system stem cells. Proc. Natl. Acad. Sci. USA 97, 14720–14725.

    PubMed  CAS  Google Scholar 

  46. Alvarez-Buylla, A., Herrera, D. G., and Wichterle, H. (2000) The subventricular zone: source of neuronal precursors for brain repair. Prog. Brain Res. 127, 1–11.

    PubMed  CAS  Google Scholar 

  47. Lillien, L. and Raphael, H. (2000) BMP and FGF regulate the development of EGF-responsive neural progenitor cells. Development 127, 4993–5005.

    PubMed  CAS  Google Scholar 

  48. Anderson, D. J. (2001) Stem cells and pattern formation in the nervous system: the possible versus the actual. Neuron 30, 19–35.

    PubMed  CAS  Google Scholar 

  49. Qian, X., Shen, Q., Goderie, S. K., et al. (2000) Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron 28, 69–80.

    PubMed  CAS  Google Scholar 

  50. Temple, S. (2001) The development of neural stem cells. Nature 414, 112–117.

    PubMed  CAS  Google Scholar 

  51. Anderson, D. J. and Axel, R. (1985) Molecular probes for the development and plasticity of neural crest derivatives. Cell 42, 649–662.

    PubMed  CAS  Google Scholar 

  52. Hu, M., Krause, D., Greaves, M., et al. (1997) Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev. 11, 774–785.

    PubMed  CAS  Google Scholar 

  53. Cao, Y., Wilcox, K. S., Martin, C. E., Rachinsky, T. L., Eberwine, J., and Dichter, M. A. (1996) Presence of mRNA for glutamic acid decarboxylase in both excitatory and inhibitory neurons. Proc. Natl. Acad. Sci. USA 93, 9844–9849.

    PubMed  CAS  Google Scholar 

  54. Arber, S., Han, B., Mendelsohn, M., Smith, M., Jessell, T. M., and Sockanathan, S. (1999) Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron 23, 659–674.

    Google Scholar 

  55. Thaler, J., Harrison, K., Sharma, K., Lettieri, K., Kehrl, J., and Pfaff, S. L. (1999) Active suppression of interneuron programs within developing motor neurons revealed by analysis of homeodomain factor HB9. Neuron 23, 675–687.

    PubMed  CAS  Google Scholar 

  56. Jan, Y. N. and Jan, L. Y. (1993) HLH proteins, fly neurogenesis, and vertebrate myogenesis. Cell 75, 827–830.

    PubMed  CAS  Google Scholar 

  57. Lo, L., Morin, X., Brunet, J. F., and Anderson, D. J. (1999) Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells. Neuron 22, 693–705.

    PubMed  CAS  Google Scholar 

  58. Lo, L., Tiveron, M. C., and Anderson, D. J. (1998) MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity. Development 125, 609–620.

    PubMed  CAS  Google Scholar 

  59. Cau, E., Gradwohl, G., Fode, C., and Guillemot, F. (1997) Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors. Development 124, 1611–1621.

    PubMed  CAS  Google Scholar 

  60. Casarosa, S., Fode, C., and Guillemot, F. (1999) Mash1 regulates neurogenesis in the ventral telencephalon. Development 126, 525–534.

    PubMed  CAS  Google Scholar 

  61. Fode, C., Ma, Q., Casarosa, S., Ang, S. L., Anderson, D. J., and Guillemot, F. (2000) A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev. 14, 67–80.

    PubMed  CAS  Google Scholar 

  62. Li, W. and LoTurco, J. J. (2000) Noggin is a negative regulator of neuronal differentiation in developing neocortex. Dev. Neurosci. 22, 68–73.

    PubMed  Google Scholar 

  63. Bonni, A., Sun, Y., Nadal-Vicens, M., et al. (1997) Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. Science 278, 477–483.

    PubMed  CAS  Google Scholar 

  64. Rajan, P. and McKay, R. D. (1998) Multiple routes to astrocytic differentiation in the CNS. J. Neurosci. 18, 3620–3629.

    PubMed  CAS  Google Scholar 

  65. Gross, R. E., Mehler, M. F., Mabie, P. C., Zang, Z., Santschi, L., and Kessler, J. A. (1996) Bone morphogenetic proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells. Neuron 17, 595–606.

    PubMed  CAS  Google Scholar 

  66. Nakashima, K. and Taga, T. (2002) Mechanisms underlying cytokine-mediated cell-fate regulation in the nervous system. Mol. Neurobiol. 25, 233–244.

    PubMed  CAS  Google Scholar 

  67. Nakashima, K., Yanagisawa, M., Arakawa, H., et al. (1999) Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science 284, 479–482.

    PubMed  CAS  Google Scholar 

  68. Sun, Y., Nadal-Vicens, M., Misono, S., et al. (2001) Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell 104, 365–376.

    PubMed  CAS  Google Scholar 

  69. Song, M. R. and Ghosh, A. (2004) FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Nat. Neurosci. 7, 229–235.

    PubMed  Google Scholar 

  70. Chang, C. and Hemmati-Brivanlou, A. (1998) Cell fate determination in embryonic ectoderm. J. Neurobiol. 36, 128–151.

    PubMed  CAS  Google Scholar 

  71. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M., and Hoffmann, J. A. (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973–983.

    PubMed  CAS  Google Scholar 

  72. 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.

    PubMed  CAS  Google Scholar 

  73. Shen, Q., Qian, X., Capela, A., and Temple, S. (1998) Stem cells in the embryonic cerebral cortex: their role in histogenesis and patterning. J. Neurobiol. 36, 162–174.

    PubMed  CAS  Google Scholar 

  74. Doe, C. Q., Fuerstenberg, S., and Peng, C. Y. (1998) Neural stem cells: from fly to vertebrates. J. Neurobiol. 36, 111–127.

    PubMed  CAS  Google Scholar 

  75. Hall, P. A. and Watt, F. M. (1989) Stem cells: the generation and maintenance of cellular diversity. Development 106, 619–633.

    PubMed  CAS  Google Scholar 

  76. Potten, C. S. and Loeffler, M. (1990) Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110, 1001–1020.

    PubMed  CAS  Google Scholar 

  77. Weiss, S., Reynolds, B. A., Vescovi, A. L., Morshead, C., Craig, C. G., and van der K. D. (1996) Is there a neural stem cell in the mammalian forebrain? Trends Neurosci. 19, 387–393.

    PubMed  CAS  Google Scholar 

  78. Lansdorp, P. M., Dragowska, W., and Mayani, H. (1993) Ontogeny-related changes in proliferative potential of human hematopoietic cells. J. Exp. Med. 178, 787–791.

    PubMed  CAS  Google Scholar 

  79. Martin, K., Kirkwood, T. B., and Potten, C. S. (1998) Age changes in stem cells of murine small intestinal crypts. Exp. Cell Res. 241, 316–323.

    PubMed  CAS  Google Scholar 

  80. Kuhn, H. G., Dickinson-Anson, H., and Gage, F. H. (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci. 16, 2027–2033.

    PubMed  CAS  Google Scholar 

  81. Lin, H. and Schagat, T. (1997) Neuroblasts: a model for the asymmetric division of stem cells. Trends Genet. 13, 33–39.

    PubMed  CAS  Google Scholar 

  82. Bryan, T. M. and Cech, T. R. (1999) Telomerase and the maintenance of chromosome ends. Curr. Opin. Cell Biol. 11, 318–324.

    PubMed  CAS  Google Scholar 

  83. Langford, L. A., Piatyszek, M. A., Xu, R., Schold, S. C., Jr., and Shay, J. W. (1995) Telomerase activity in human brain tumours. Lancet 346, 1267–1268.

    PubMed  CAS  Google Scholar 

  84. Le, S., Zhu, J. J., Anthony, D. C., Greider, C. W., and Black, P. M. (1998) Telomerase activity in human gliomas. Neurosurgery 42, 1120–1124; discussion 1124–1125.

    PubMed  CAS  Google Scholar 

  85. Weil, R. J., Wu, Y. Y., Vortmeyer, A. O., et al. (1999) Telomerase activity in micro-dissected human gliomas. Mod. Pathol. 12, 41–46.

    PubMed  CAS  Google Scholar 

  86. Counter, C. M., Hahn, W. C., Wei, W., et al. (1998) Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc. Natl. Acad. Sci. USA 95, 14723–14728.

    PubMed  CAS  Google Scholar 

  87. Roy, N. S., Nakano, T., Keyoung, H. M., et al. (2004) Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cord. Nat. Bio-technol. 22, 297–305.

    CAS  Google Scholar 

  88. Blasco, M. A., Funk, W., Villeponteau, B., and Greider, C. W. (1995) Functional characterization and developmental regulation of mouse telomerase RNA. Science 269, 1267–1270.

    PubMed  CAS  Google Scholar 

  89. Blasco, M. A., Lee, H. W., Hande, M. P., et al. (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34.

    PubMed  CAS  Google Scholar 

  90. Dye, C. A., Lee, J. K., Atkinson, R. C., Brewster, R., Han, P. L., and Bellen, H. J. (1998) The Drosophila sanpodo gene controls sibling cell fate and encodes a tropomodulin homolog, an actin/tropomyosin-associated protein. Development 125, 1845–1856.

    PubMed  CAS  Google Scholar 

  91. Bornemann, A., Maier, F., and Kuschel, R. (1999) Satellite cells as players and targets in normal and diseased muscle. Neuropediatrics 30, 167–175.

    PubMed  CAS  Google Scholar 

  92. Schultz, E. and McCormick, K. M. (1994) Skeletal muscle satellite cells. Rev. Physiol. Biochem. Pharmacol. 123, 213–257.

    PubMed  CAS  Google Scholar 

  93. Doerner, P. (1998) Root development: quiescent center not so mute after all. Curr. Biol. 8, R42–44.

    PubMed  CAS  Google Scholar 

  94. Morrison, S. J. and Weissman, I. L. (1994) The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1, 661–673.

    PubMed  CAS  Google Scholar 

  95. Doetsch, F. (2003) The glial identity of neural stem cells. Nat. Neurosci. 6, 1127–1134.

    PubMed  CAS  Google Scholar 

  96. Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703–716.

    PubMed  CAS  Google Scholar 

  97. Doetsch, F., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci. 17, 5046–5061.

    PubMed  CAS  Google Scholar 

  98. Doetsch, F., Petreanu, L., Caille, I., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36, 1021–1034.

    PubMed  CAS  Google Scholar 

  99. Potten, C. S. (1998) Stem cells in gastrointestinal epithelium: numbers, characteristics and death. Philos. Trans. R. Soc. Lond. B Biol. Sci. 353, 821–830.

    PubMed  CAS  Google Scholar 

  100. Whetton, A. D. and Graham, G. J. (1999) Homing and mobilization in the stem cell niche. Trends Cell Biol. 9, 233–238.

    PubMed  CAS  Google Scholar 

  101. Jacobson, M. (1991) Developmental Neurobiology. Plenum Press, New York.

    Google Scholar 

  102. Takahashi, T., Nowakowski, R. S., and Caviness, V. S., Jr. (1995) The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J. Neurosci. 15, 6046–6057.

    PubMed  CAS  Google Scholar 

  103. Morshead, C. M., Craig, C. G., and van der Kooy, D. (1998) In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain. Development 125, 2251–2261.

    PubMed  CAS  Google Scholar 

  104. Garcia-Verdugo, J. M., Doetsch, F., Wichterle, H., Lim, D. A., and Alvarez-Buylla, A. (1998) Architecture and cell types of the adult subventricular zone: in search of the stem cells. J. Neurobiol. 36, 234–248.

    PubMed  CAS  Google Scholar 

  105. Weiss, S. and van der K. D. (1998) CNS stem cells: where’s the biology (a.k.a. beef)? J. Neurobiol. 36, 307–314.

    PubMed  CAS  Google Scholar 

  106. Knoblich, J. A., Jan, L. Y., and Jan, Y. N. (1995) Asymmetric segregation of Numb and Prospero during cell division. Nature 377, 624–627.

    PubMed  CAS  Google Scholar 

  107. Hirata, J., Nakagoshi, H., Nabeshima, Y., and Matsuzaki, F. (1995) Asymmetric segregation of the homeodomain protein Prospero during Drosophila development. Nature 377, 627–630.

    PubMed  CAS  Google Scholar 

  108. Doe, C. Q., Chu-LaGraff, Q., Wright, D. M., and Scott, M. P. (1991) The prospero gene specifies cell fates in the Drosophila central nervous system. Cell 65, 451–464.

    PubMed  CAS  Google Scholar 

  109. Li, L. and Vaessin, H. (2000) Pan-neural Prospero terminates cell proliferation during Drosophila neurogenesis. Genes Dev. 14, 147–151.

    PubMed  CAS  Google Scholar 

  110. Buescher, M., Yeo, S. L., Udolph, G., et al. (1998) Binary sibling neuronal cell fate decisions in the Drosophila embryonic central nervous system are nonstochastic and require inscuteable-mediated asymmetry of ganglion mother cells. Genes Dev. 12, 1858–1870.

    PubMed  CAS  Google Scholar 

  111. Wai, P., Truong, B., and Bhat, K. M. (1999) Cell division genes promote asymmetric interaction between Numb and Notch in the Drosophila CNS. Development 126, 2759–2770.

    PubMed  CAS  Google Scholar 

  112. Abdelilah-Seyfried, S., Chan, Y. M., Zeng, C., et al. (2000) A gain-of-function screen for genes that affect the development of the Drosophila adult external sensory organ. Genetics 155, 733–752.

    PubMed  CAS  Google Scholar 

  113. Berdnik, D., Torok, T., Gonzalez-Gaitan, M., and Knoblich, J. A. (2002) The endocytic protein alpha-Adaptin is required for numb-mediated asymmetric cell division in Drosophila. Dev. Cell 3, 221–231.

    PubMed  CAS  Google Scholar 

  114. Schober, M., Schaefer, M., and Knoblich, J. A. (1999) Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts. Nature 402, 548–551.

    PubMed  CAS  Google Scholar 

  115. Wodarz, A., Ramrath, A., Kuchinke, U., and Knust, E. (1999) Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts. Nature 402, 544–547.

    PubMed  CAS  Google Scholar 

  116. Chia, W., Kraut, R., Li, P., Yang, X., and Zavortink, M. (1997) On the roles of inscuteable in asymmetric cell divisions in Drosophila. Cold Spring Harb. Symp. Quant. Biol. 62, 79–87.

    PubMed  CAS  Google Scholar 

  117. Wodarz, A., Ramrath, A., Grimm, A., and Knust, E. (2000) Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J. Cell Biol. 150, 1361–1374.

    PubMed  CAS  Google Scholar 

  118. Schaefer, M. and Knoblich, J. A. (2001) Protein localization during asymmetric cell division. Exp. Cell Res. 271, 66–74.

    PubMed  CAS  Google Scholar 

  119. Yu, F., Morin, X., Cai, Y., Yang, X., and Chia, W. (2000) Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell 100, 399–409.

    PubMed  CAS  Google Scholar 

  120. Kraut, R., Chia, W., Jan, L. Y., Jan, Y. N., and Knoblich, J. A. (1996) Role of inscuteable in orienting asymmetric cell divisions in Drosophila. Nature 383, 50–55.

    PubMed  CAS  Google Scholar 

  121. Broadus, J., Fuerstenberg, S., and Doe, C. Q. (1998) Staufen-dependent localization of prospero mRNA contributes to neuroblast daughter-cell fate. Nature 391, 792–795.

    PubMed  CAS  Google Scholar 

  122. Schuldt, A. J., Adams, J. H., Davidson, C. M., et al. (1998) Miranda mediates asymmetric protein and RNA localization in the developing nervous system. Genes Dev. 12, 1847–1857.

    PubMed  CAS  Google Scholar 

  123. Shen, C. P., Knoblich, J. A., Chan, Y. M., Jiang, M. M., Jan, L. Y., and Jan, Y. N. (1998) Miranda as a multidomain adapter linking apically localized Inscuteable and basally localized Staufen and Prospero during asymmetric cell division in Drosophila. Genes Dev. 12, 1837–1846.

    PubMed  CAS  Google Scholar 

  124. Ikeshima-Kataoka, H., Skeath, J. B., Nabeshima, Y., Doe, C. Q., and Matsuzaki, F. (1997) Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions. Nature 390, 625–629.

    PubMed  CAS  Google Scholar 

  125. Lu, B., Rothenberg, M., Jan, L. Y., and Jan, Y. N. (1998) Partner of Numb colocalizes with Numb during mitosis and directs Numb asymmetric localization in Drosophila neural and muscle progenitors. Cell 95, 225–235.

    PubMed  CAS  Google Scholar 

  126. Wodarz, A. and Huttner, W. B. (2003) Asymmetric cell division during neurogenesis in Drosophila and vertebrates. Mech. Dev. 120, 1297–1309.

    PubMed  CAS  Google Scholar 

  127. Weigmann, A., Corbeil, D., Hellwig, A., and Huttner, W. B. (1997) Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc. Natl. Acad. Sci. USA 94, 12425–12430.

    PubMed  CAS  Google Scholar 

  128. Chenn, A., Zhang, Y. A., Chang, B. T., and McConnell, S. K. (1998) Intrinsic polarity of mammalian neuroepithelial cells. Mol. Cell Neurosci. 11, 183–193.

    PubMed  CAS  Google Scholar 

  129. Aaku-Saraste, E., Hellwig, A., and Huttner, W. B. (1996) Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure—remodeling of the neuroepithelium prior to neurogenesis. Dev. Biol. 180, 664–679.

    PubMed  CAS  Google Scholar 

  130. Zhadanov, A. B., Provance, D. W., Jr., Speer, C. A., et al. (1999) Absence of the tight junctional protein AF-6 disrupts epithelial cell-cell junctions and cell polarity during mouse development. Curr. Biol. 9, 880–888.

    PubMed  CAS  Google Scholar 

  131. Manabe, N., Hirai, S., Imai, F., Nakanishi, H., Takai, Y., and Ohno, S. (2002) Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells. Dev. Dyn. 225, 61–69.

    PubMed  CAS  Google Scholar 

  132. Stuckmann, I., Weigmann, A., Shevchenko, A., Mann, M., and Huttner, W. B. (2001) Ephrin B1 is expressed on neuroepithelial cells in correlation with neocortical neurogenesis. J. Neurosci. 21, 2726–2737.

    PubMed  CAS  Google Scholar 

  133. Takekuni, K., Ikeda, W., Fujito, T., et al. (2003) Direct binding of cell polarity protein PAR-3 to cell-cell adhesion molecule nectin at neuroepithelial cells of developing mouse. J. Biol. Chem. 278, 5497–5500.

    PubMed  CAS  Google Scholar 

  134. Zhong, W., Feder, J. N., Jiang, M. M., Jan, L. Y., and Jan, Y. N. (1996) Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis. Neuron 17, 43–53.

    PubMed  CAS  Google Scholar 

  135. Wakamatsu, Y., Maynard, T. M., Jones, S. U., and Weston, J. A. (1999) NUMB localizes in the basal cortex of mitotic avian neuroepithelial cells and modulates neuronal differentiation by binding to NOTCH-1. Neuron 23, 71–81.

    PubMed  CAS  Google Scholar 

  136. Chenn, A. and McConnell, S. K. (1995) Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis. Cell 82, 631–641.

    PubMed  CAS  Google Scholar 

  137. Haydar, T. F., Ang, E., Jr., and Rakic, P. (2003) Mitotic spindle rotation and mode of cell division in the developing telencephalon. Proc. Natl. Acad. Sci. USA 100, 2890–2895.

    PubMed  CAS  Google Scholar 

  138. Kornack, D. R. and Rakic, P. (1995) Radial and horizontal deployment of clonally related cells in the primate neocortex: relationship to distinct mitotic lineages. Neuron 15, 311–321.

    PubMed  CAS  Google Scholar 

  139. Reid, C. B., Tavazoie, S. F., and Walsh, C. A. (1997) Clonal dispersion and evidence for asymmetric cell division in ferret cortex. Development 124, 2441–2450.

    PubMed  CAS  Google Scholar 

  140. Bhat, K. M. (1998) Cell-cell signaling during neurogenesis: some answers and many questions. Int. J. Dev. Biol. 42, 127–139.

    PubMed  CAS  Google Scholar 

  141. Ware, M. L., Tavazoie, S. F., Reid, C. B., and Walsh, C. A. (1999) Coexistence of widespread clones and large radial clones in early embryonic ferret cortex. Cereb. Cortex 9, 636–645.

    PubMed  CAS  Google Scholar 

  142. 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.

    PubMed  CAS  Google Scholar 

  143. Noctor, S. C., Martinez-Cerdeno, V., Ivic, L., and Kriegstein, A. R. (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat. Neurosci. 7, 136–144.

    PubMed  CAS  Google Scholar 

  144. Miyata, T., Kawaguchi, A., Okano, H., and Ogawa, M. (2001) Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31, 727–741.

    PubMed  CAS  Google Scholar 

  145. Qian, X., Goderie, S. K., Shen, Q., Stern, J. H., and Temple, S. (1998) Intrinsic programs of patterned cell lineages in isolated vertebrate CNS ventricular zone cells. Development 125, 3143–3152.

    PubMed  CAS  Google Scholar 

  146. Shen, Q., Zhong, W., Jan, Y. N., and Temple, S. (2002) Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. Development 129, 4843–4853.

    PubMed  CAS  Google Scholar 

  147. Li, H. S., Wang, D., Shen, Q., et al. (2003) Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis. Neuron 40, 1105–1118.

    PubMed  CAS  Google Scholar 

  148. Cayouette, M., Whitmore, A. V., Jeffery, G., and Raff, M. (2001) Asymmetric segregation of Numb in retinal development and the influence of the pigmented epithelium. J. Neurosci. 21, 5643–5651.

    PubMed  CAS  Google Scholar 

  149. Seecof, R. L., Donady, J. J., and Teplitz, R. L. (1973) Differentiation of Drosophila neuroblasts to form ganglion-like clusters of neurons in vitro. Cell Differ. 2, 143–149.

    PubMed  CAS  Google Scholar 

  150. Huff, R., Furst, A., and Mahowald, A. P. (1989) Drosophila embryonic neuroblasts in culture: autonomous differentiation of specific neurotransmitters. Dev. Biol. 134, 146–157.

    PubMed  CAS  Google Scholar 

  151. Lu, B., Roegiers, F., Jan, L. Y., and Jan, Y. N. (2001) Adherens junctions inhibit asymmetric division in the Drosophila epithelium. Nature 409, 522–525.

    PubMed  CAS  Google Scholar 

  152. Fuchs, E. and Segre, J. A. (2000) Stem cells: a new lease on life. Cell 100, 143–155.

    PubMed  CAS  Google Scholar 

  153. Doetsch, F. (2003) A niche for adult neural stem cells. Curr. Opin. Genet. Dev. 13, 543–550.

    PubMed  CAS  Google Scholar 

  154. Steindler, D. A., Kadrie, T., Fillmore, H., and Thomas, L. B. (1996) The subependymal zone: “brain marrow.” Prog. Brain Res. 108, 349–363.

    PubMed  CAS  Google Scholar 

  155. Murphy, M., Reid, K., Dutton, R., Brooker, G., and Bartlett, P. F. (1997) Neural stem cells. J. Invest. Dermatol. Symp. Proc. 2, 8–13.

    CAS  Google Scholar 

  156. Lillien, L. (1997) Neural development: instructions for neural diversity. Curr. Biol. 7, R168–R171.

    PubMed  CAS  Google Scholar 

  157. Mehler, M. F. and Gokhan, S. (1999) Postnatal cerebral cortical multipotent progenitors: regulatory mechanisms and potential role in the development of novel neural regenerative strategies. Brain Pathol. 9, 515–526.

    PubMed  CAS  Google Scholar 

  158. Olsson, M., Bjerregaard, K., Winkler, C., Gates, M., Bjorklund, A., and Campbell, K. (1998) Incorporation of mouse neural progenitors transplanted into the rat embryonic forebrain is developmentally regulated and dependent on regional and adhesive properties. Eur. J. Neurosci. 10, 71–85.

    PubMed  CAS  Google Scholar 

  159. Gage, F. H. (2000) Mammalian neural stem cells. Science 287, 1433–1438.

    PubMed  CAS  Google Scholar 

  160. Chmielnicki, E., Benraiss, A., Economides, A. N., and Goldman, S. A. (2004) Adeno-virally expressed noggin and brain-derived neurotrophic factor cooperate to induce new medium spiny neurons from resident progenitor cells in the adult striatal ventricular zone. J. Neurosci. 24, 2133–2142.

    PubMed  CAS  Google Scholar 

  161. Alvarez-Buylla, A. and Lim, D. A. (2004) For the long run; maintaining germinal niches in the adult brain. Neuron 41, 683–686.

    PubMed  CAS  Google Scholar 

  162. Capela, A. and Temple, S. (2002) LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron 35, 865–875.

    PubMed  Google Scholar 

  163. Louissaint, A., Jr., Rao, S., Leventhal, C., and Goldman, S. A. (2002) Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron 34, 945–960.

    PubMed  CAS  Google Scholar 

  164. Palmer, T. D., Willhoite, A. R., and Gage, F. H. (2000) Vascular niche for adult hippocampal neurogenesis. J. Comp. Neurol. 425, 479–494.

    PubMed  CAS  Google Scholar 

  165. Shen, Q., Goderie, S. K., Jin, L., et al. (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304, 1338–1340.

    PubMed  CAS  Google Scholar 

  166. Milner, L. A., Kopan, R., Martin, D. I., and Bernstein, I. D. (1994) A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors. Blood 83, 2057–2062.

    PubMed  CAS  Google Scholar 

  167. Varnum-Finney, B., Purton, L. E., Yu, M., et al. (1998) The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells. Blood 91, 4084–4091.

    PubMed  CAS  Google Scholar 

  168. Jones, P., May, G., Healy, L., et al. (1998) Stromal expression of Jagged 1 promotes colony formation by fetal hematopoietic progenitor cells. Blood 92, 1505–1511.

    PubMed  CAS  Google Scholar 

  169. Li, L., Milner, L. A., Deng, Y., et al. (1998) The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch 1. Immunity 8, 43–55.

    PubMed  CAS  Google Scholar 

  170. Walker, L., Lynch, M., Silverman, S., et al. (1999) The Notch/Jagged pathway inhibits proliferation of human hematopoietic progenitors in vitro. Stem Cells 17, 162–171.

    PubMed  CAS  Google Scholar 

  171. Lewis, J. (1998) Notch signalling and the control of cell fate choices in vertebrates. Semin. Cell Dev. Biol. 9, 583–589.

    PubMed  CAS  Google Scholar 

  172. Campos-Ortega, J. A. (1995) Genetic mechanisms of early neurogenesis in Drosophila melanogaster. Mol. Neurobiol. 10, 75–89.

    PubMed  CAS  Google Scholar 

  173. Skeath, J. B. and Doe, C. Q. (1998) Sanpodo and Notch act in opposition to Numb to distinguish sibling neuron fates in the Drosophila CNS. Development 125, 1857–1865.

    PubMed  CAS  Google Scholar 

  174. Gaiano, N., Nye, J. S., and Fishell, G. (2000) Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26, 395–404.

    PubMed  CAS  Google Scholar 

  175. Berezovska, O., Xia, M. Q., and Hyman, B. T. (1998) Notch is expressed in adult brain, is coexpressed with presenilin-1, and is altered in Alzheimer disease. J. Neuropathol. Exp. Neurol. 57, 738–745.

    PubMed  CAS  Google Scholar 

  176. Sestan, N., Artavanis-Tsakonas, S., and Rakic, P. (1999) Contact-dependent inhibition of cortical neurite growth mediated by notch signaling. Science 286, 741–746.

    PubMed  CAS  Google Scholar 

  177. Wang, S., Sdrulla, A. D., diSibio, G., et al. (1998) Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 21, 63–75.

    PubMed  Google Scholar 

  178. Cameron, H. A., Hazel, T. G., and McKay, R. D. (1998) Regulation of neurogenesis by growth factors and neurotransmitters. J. Neurobiol. 36, 287–306.

    PubMed  CAS  Google Scholar 

  179. Shipley, G. D., Keeble, W. W., Hendrickson, J. E., Coffey, R. J., Jr., and Pittelkow, M. R. (1989) Growth of normal human keratinocytes and fibroblasts in serum-free medium is stimulated by acidic and basic fibroblast growth factor. J. Cell Physiol. 138, 511–518.

    PubMed  CAS  Google Scholar 

  180. Reddi, A. H. and Cunningham, N. S. (1990) Bone induction by osteogenin and bone morphogenetic proteins. Biomaterials 11, 33–34.

    PubMed  CAS  Google Scholar 

  181. Fuchs, E. and Byrne, C. (1994) The epidermis: rising to the surface. Curr. Opin. Genet. Dev. 4, 725–736.

    PubMed  CAS  Google Scholar 

  182. Donovan, P. J. (1994) Growth factor regulation of mouse primordial germ cell development. Curr. Top. Dev. Biol. 29, 189–225.

    PubMed  CAS  Google Scholar 

  183. Allouche, M. (1995) Basic fibroblast growth factor and hematopoiesis. Leukemia 9, 937–942.

    PubMed  CAS  Google Scholar 

  184. McKay, R. (1997) Stem cells in the central nervous system. Science 276, 66–71.

    PubMed  CAS  Google Scholar 

  185. Burgess, A. W. (1998) Growth control mechanisms in normal and transformed intestinal cells. Philos. Trans. R. Soc. Lond. B Biol. Sci. 353, 903–909.

    PubMed  CAS  Google Scholar 

  186. Murphy, M. S. (1998) Growth factors and the gastrointestinal tract. Nutrition 14, 771–774.

    PubMed  CAS  Google Scholar 

  187. Benfey, P. N. (1999) Stem cells: a tale of two kingdoms. Curr. Biol. 9, R171–R172.

    PubMed  CAS  Google Scholar 

  188. Cox, D. N., Chao, A., and Lin, H. (2000) piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development 127, 503–514.

    PubMed  CAS  Google Scholar 

  189. Nakamura, M., Okano, H., Blendy, J. A., and Montell, C. (1994) Musashi, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron 13, 67–81.

    PubMed  CAS  Google Scholar 

  190. Good, P., Yoda, A., Sakakibara, S., et al. (1998) The human Musashi homolog 1 (MSI1) gene encoding the homologue of Musashi/Nrp-1, a neural RNA-binding protein putatively expressed in CNS stem cells and neural progenitor cells. Genomics 52, 382–384.

    PubMed  CAS  Google Scholar 

  191. Kaneko, Y., Sakakibara, S., Imai, T., et al. (2000) Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev. Neurosci. 22, 139–153.

    PubMed  CAS  Google Scholar 

  192. Lendahl, U., Zimmerman, L. B., and McKay, R. D. (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60, 585–595.

    PubMed  CAS  Google Scholar 

  193. 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.

    PubMed  CAS  Google Scholar 

  194. Shi, Y., Chichung Lie, D., Taupin, P., et al. (2004) Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature 427, 78–83.

    PubMed  CAS  Google Scholar 

  195. Cheshier, S. H., Morrison, S. J., Liao, X., and Weissman, I. L. (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc. Natl. Acad. Sci. USA 96, 3120–3125.

    PubMed  CAS  Google Scholar 

  196. 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.

    PubMed  CAS  Google Scholar 

  197. Dvorak, P., Hampl, A., Jirmanova, L., Pacholikova, J., and Kusakabe, M. (1998) Embryoglycan ectodomains regulate biological activity of FGF-2 to embryonic stem cells. J. Cell Sci. 111(Pt 19), 2945–2952.

    PubMed  CAS  Google Scholar 

  198. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., et al. (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418, 41–49.

    PubMed  CAS  Google Scholar 

  199. Ramalho-Santos, M., Yoon, S., Matsuzaki, Y., Mulligan, R. C., and Melton, D. A. (2002) “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science 298, 597–600.

    PubMed  CAS  Google Scholar 

  200. Ivanova, N. B., Dimos, J. T., Schaniel, C., Hackney, J. A., Moore, K. A., and Lemischka, I. R. (2002) A stem cell molecular signature. Science 298, 601–604.

    PubMed  CAS  Google Scholar 

  201. Burns, C. E. and Zon, L. I. (2002) Portrait of a stem cell. Dev. Cell 3, 612–613.

    PubMed  CAS  Google Scholar 

  202. Petkov, P. M., Zavadil, J., Goetz, D., et al. (2004) Gene expression pattern in hepatic stem/progenitor cells during rat fetal development using complementary DNA micro-arrays. Hepatology 39, 617–627.

    PubMed  CAS  Google Scholar 

  203. Ahn, J. I., Lee, K. H., Shin, D. M., et al. (2004) Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons. Dev. Biol. 265, 491–501.

    PubMed  CAS  Google Scholar 

  204. Wieczorek, G., Steinhoff, C., Schulz, R., et al. (2003) Gene expression profile of mouse bone marrow stromal cells determined by cDNA microarray analysis. Cell Tissue Res. 311, 227–237.

    PubMed  CAS  Google Scholar 

  205. Bhattacharya, B., Miura, T., Brandenberg, R., et al. (2004) Gene expression in human embryonic stem cell lines: unique molecular signature. Blood 103, 2956–2964.

    PubMed  CAS  Google Scholar 

  206. Fortunel, N. O., Otu, H. H., Ng, H. H., et al. (2003) Comment on “’stemness’: transcriptional profiling of embryonic and adult stem cells” and “a stem cell molecular signature.” Science 302, 393; author reply 393.

    PubMed  CAS  Google Scholar 

  207. Luo, Y., Cai, J., Liu, Y., Xue, H., Chrest, F. J., Wersto, R. P., and Rao, M. (2002) Microarray analysis of selected genes in neural stem and progenitor cells. J. Neurochem. 83, 1481–1497.

    PubMed  CAS  Google Scholar 

  208. 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, 14506–14511.

    PubMed  CAS  Google Scholar 

  209. Luo, Y., Cai, J., Ginis, I., et al. (2003) Designing, testing, and validating a focused stem cell microarray for characterization of neural stem cells and progenitor cells. Stem Cells 21, 575–587.

    PubMed  CAS  Google Scholar 

  210. Karsten, S. L., Kudo, L. C., Jackson, R., Sabatti, C., Kornblum, H. I., and Geschwind, D. H. (2003) Global analysis of gene expression in neural progenitors reveals specific cell-cycle, signaling, and metabolic networks. Dev. Biol. 261, 165–182.

    PubMed  CAS  Google Scholar 

  211. Oliver, T. G., Grasfeder, L. L., Carroll, A. L., et al. (2003) Transcriptional profiling of the Sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors. Proc. Natl. Acad. Sci. USA 100, 7331–7336.

    PubMed  CAS  Google Scholar 

  212. Livesey, F. J., Young, T. L., and Cepko, C. L. (2004) An analysis of the gene expression program of mammalian neural progenitor cells. Proc. Natl. Acad. Sci. USA 101, 1374–1379.

    PubMed  CAS  Google Scholar 

  213. Shah, N. M. and Anderson, D. J. (1997) Integration of multiple instructive cues by neural crest stem cells reveals cell-intrinsic biases in relative growth factor responsiveness. Proc. Natl. Acad. Sci. USA 94, 11369–11374.

    PubMed  CAS  Google Scholar 

  214. Park, J. K., Williams, B. P., Alberta, J. A., and Stiles, C. D. (1999) Bipotent cortical progenitor cells process conflicting cues for neurons and glia in a hierarchical manner. J. Neurosci. 19, 10383–10389.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Neuroscience and Neuropharmacology, Albany Medical Center, Albany, NY

    Sally Temple

Authors
  1. Sally Temple
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. National Institute on Aging, Baltimore, MD

    Mahendra S. Rao MBBS, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Temple, S. (2006). Defining Neural Stem Cells and Their Role in Normal Development of the Nervous System. In: Rao, M.S. (eds) Neural Development and Stem Cells. Contemporary Neuroscience. Humana Press. https://doi.org/10.1385/1-59259-914-1:001

Download citation

Publish with us

Policies and ethics

Search

Navigation