Molecular Neurobiology

, Volume 27, Issue 1, pp 73–98 | Cite as

Mammalian neural stem-cell renewal

Nature versus nurture
Article

Abstract

Recent data show that the final events of mammalian brain organogenesis may depend in part on the direct control of neural stem cell (NSC) proliferation and survival. Environmental and intrinsic factors play a role throughout development and during adulthood to regulate NSC proliferation. The NSCs acquire new competences throughout development, including adulthood, and this change in competence is region-specific. The factors controlling NSC survival, undifferentiated state, proliferation, and cell-cycle number are beginning to be identified, but the links between them remain unclear. However, current knowledge should help to formulate an understanding of how a stem cell can generate a new stem cell.

Index Entries

Stem cell neural precursors neurogenesis retina spinal cord telencephalon neurons glia 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Turner D. L. and Cepko C. L. (1987) A common progenitor for neurons and glia persists in rat retina late in development. Nature 328, 131–136.PubMedGoogle Scholar
  2. 2.
    Reid C. B. and Tavazoie S. F., and Walsh C. A. (1997) Clonal dispersion and evidence for asymmetric cell division in ferret cortex. Development 124, 2441–2450.PubMedGoogle Scholar
  3. 3.
    Potten C. S. and Loeffler M. (1990) Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. tainties. Lessons for and from the crypt. Development 110, 1001–1020.PubMedGoogle Scholar
  4. 4.
    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.PubMedGoogle Scholar
  5. 5.
    Alvarez-Buylla A., Garcia-Verdugo J. M., and Tramontin A. D. (2001) A unified hypothesis on the lineage of neural stem cells. Nat. Rev. Neurosci. 2, 287–293.PubMedGoogle Scholar
  6. 6.
    Morshead C. M. and van der Kooy D. (2001) A new ‘spin’ on neural stem cells? Curr. Opin. Neurobiol. 11, 59–65.PubMedGoogle Scholar
  7. 7.
    Sommer L. and Rao M. (2002) Neural stem cells and regulation of cell number. Prog. Neurobiol. 66, 1–18.PubMedGoogle Scholar
  8. 8.
    McKay R. (2000) Stem cells and the cellular organization of the brain. J. Neurosci. Res. 59, 298–300.PubMedGoogle Scholar
  9. 9.
    Gage F. H. (2000) Mammalian neural stem cells. Science 287, 1433–1438.PubMedGoogle Scholar
  10. 10.
    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.PubMedGoogle Scholar
  11. 11.
    Livesey F. J. and Cepko C. L. (2001) Vertebrate neural cell-fate determination: lessons from the retina. Nat. Rev. Neurosci. 2, 109–118.PubMedGoogle Scholar
  12. 12.
    Reh T. A. and Levine E. M. (1998) Multipotential stem cells and progenitors in the vertebrate retina. J. Neurobiol. 36, 206–220.PubMedGoogle Scholar
  13. 13.
    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.PubMedGoogle Scholar
  14. 14.
    Vescovi A. L., Parati E. A., Gritti A., Poulin P., Ferrario M., Wanke E., et al. (1999) Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp. Neurol. 156, 71–83.PubMedGoogle Scholar
  15. 15.
    Ciccolini F. (2001) Identification of two distinct types of multipotent neural precursors that appear sequentially during CNS development. Mol. Cell. Neurosci. 17, 895–907.PubMedGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    Tropepe V., Sibilia M., Ciruna B. G., Rossant J., Wagner E. F., and van der K. D. (1999) Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev. Biol. 208, 166–188.PubMedGoogle Scholar
  18. 18.
    Altman J. and Das G. D. (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J. Comp. Neurol. 124, 319–335.PubMedGoogle Scholar
  19. 19.
    Bayer S. A., Yackel J. W., and Puri P. S. (1982) Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life. Science 216, 890–892.PubMedGoogle Scholar
  20. 20.
    Lois C. and Alvarez-Buylla A. (1993) Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc. Natl. Acad. Sci. USA 90, 2074–2077.PubMedGoogle Scholar
  21. 21.
    Lois C. and Alvarez-Buylla A. (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264, 1145–1148.PubMedGoogle Scholar
  22. 22.
    Luskin M. B. (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11, 173–189.PubMedGoogle Scholar
  23. 23.
    Reynolds B. A. and Weiss S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707–1710.PubMedGoogle Scholar
  24. 24.
    Palmer T. D., Takahashi J., and Gage F. H. (1997) The adult rat hippocampus contains primordial neural stem cells. Mol. Cell. Neurosci. 8, 389–404.PubMedGoogle Scholar
  25. 25.
    Tropepe V., Coles B. L., Chiasson B. J., Horsford D. J., Elia A. J., McInnes R. R., et al. (2000) Retinal stem cells in the adult mammalian eye. Science 287, 2032–2036.PubMedGoogle Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    Johansson C. B., Momma S., Clarke D. L., Risling M., Lendahl U., and Frisen J. (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96, 25–34.PubMedGoogle Scholar
  28. 28.
    Chiasson B. J., Tropepe V., Morshead C. M., and van der Kooy D. (1999) Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J. Neurosci. 19, 4462–4471.PubMedGoogle Scholar
  29. 29.
    Ahmad I., Dooley C. M., and Afiat S. (1998) Involvement of Mash 1 in EGF-mediated regulation of differentiation in the vertebrate retina. Dev. Biol. 194, 86–98.PubMedGoogle Scholar
  30. 30.
    Ciccolini F. and Svendsen C. N. (1998) Fibroblast growth factor 2 (FGF-2) promotes acquisition of epidermal growth factor (EGF) responsiveness in mouse striatal precursor cells: identification of neural precursors responding to both EGF and FGF-2. J. Neursci. 18, 7869–7880.Google Scholar
  31. 31.
    Arsenijevic Y., Weiss S., Schneider B., and Aebischer P. (2001) Insulin-like growth factor-1 is necessary for neural stem cell proliferation and demonstrates distinct actions of epidermal growth factor and fibroblast growth factor-2. J. Neurosci. 21, 7194–7202.PubMedGoogle Scholar
  32. 32.
    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.PubMedGoogle Scholar
  33. 33.
    Gritti A., Cova L., Parati E. A., Galli R., and Vescovi A. L. (1995) Basic fibroblast growth factor supports the proliferation of epidermal growth factor-generated neuronal precursor cells of the adult mouse CNS. Neurosci. Lett. 185, 151–154.PubMedGoogle Scholar
  34. 34.
    Deng C. X., Wynshaw-Boris A., Shen M. M., Daugherty C., Ornitz D. M., and Leder P. (1994) Murine FGFR-1 is required for early postimplantation growth and axial organization. Genes Dev. 8, 3045–3057.PubMedGoogle Scholar
  35. 35.
    Sibilia M., Steinbach J. P., Stingl L., Aguzzi A., and Wagner E. F. (1998) A strain-independent postnatal neurodegeneration in mice lacking the EGF receptor. EMBO J. 17, 719–731.PubMedGoogle Scholar
  36. 36.
    Yamaguchi T. P., Harpal K., Henkemeyer M., and Rossant J. (1994) fgfr-1 is required for embryonic growth and mesodermal patterning during mouse gastrulation. Genes Dev. 8, 3032–3044.PubMedGoogle Scholar
  37. 37.
    Burrows R. C., Wancio D., Levitt P., and Lillien L. (1997) Response diversity and the timing of progenitor cell maturation are regulated by developmental changes in EGFR expression in the cortex. Neuron 19, 251–267.PubMedGoogle Scholar
  38. 38.
    Lillien L. and Raphael H. (2000) BMP and FGF regulate the development of EGF-responsive neural progenitor cells. Development 127, 4993–5005.PubMedGoogle Scholar
  39. 39.
    Zhu G., Mehler M. F., Mabie P. C., and Kessler J. A. (1999) Developmental changes in progenitor cell responsiveness to cytokines. J. Neurosci. Res. 56, 131–145.PubMedGoogle Scholar
  40. 40.
    Baker J., Liu J. P., Robertson E. J., and Efstratiadis A. (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75, 73–82.PubMedGoogle Scholar
  41. 41.
    Beck K. D., Powell-Braxton L., Widmer H. R., Valverde J., and Hefti F. (1995) Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron 14, 717–730.PubMedGoogle Scholar
  42. 42.
    Liu J. P., Baker J., Perkins A. S., Robertson E. J., and Efstratiadis A. (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75, 59–72.PubMedGoogle Scholar
  43. 43.
    Diaz B., Serna J., de Pablo F., and de la Rosa E. J. (2000) In vivo regulation of cell death by embryonic (pro)insulin and the insulin receptor during early retinal neurogenesis. Development 127, 1641–1649.PubMedGoogle Scholar
  44. 44.
    Fischer A. J., Dierks B. D., and Reh T. A. (2002) Exogenous growth factors induce the production of ganglion cells at the retinal margin. Development 129, 2283–2291.PubMedGoogle Scholar
  45. 45.
    Harris W. A. (1997) Cellular diversification in the vertebrate retina. Curr. Opin. Genet. Dev. 7, 651–658.PubMedGoogle Scholar
  46. 46.
    Carpenter M. K., Cui X., Hu Z. Y., Jackson J., Sherman S., Seiger A., et al. (1999) In vitro expansion of a multipotent population of human neural progenitor cells. Exp. Neurol. 158, 265–278.PubMedGoogle Scholar
  47. 47.
    Emerich D. F., Winn S. R., Hantraye P. M., Peschanski M., Chen E. Y., Chu Y., et al. (1997) Protective effect of encapsulated cells producting neurotrophic factor CNTF in a monkey model of Huntington’s disease. Nature 386, 395–399.PubMedGoogle Scholar
  48. 48.
    Ip N. Y., Li Y. P., van de Stadt I., Panayotatos N., Alderson R. F., and Lindsay R. M. (1991) Ciliary neurotrophic factor enhances neuronal survival in embryonic rat hippocampal cultures. J. Neurosci. 11, 3124–3134.PubMedGoogle Scholar
  49. 49.
    Larkfors L., Lindsay R. M., and Alderson R. F. (1994) Ciliary neurotrophic factor enhances the survival of Purkinje cells in vitro. Eur. J. Neurosci. 6, 1015–1025.PubMedGoogle Scholar
  50. 50.
    Shimazaki T., Shingo T., and Weiss S. (2001) The ciliary neurotrophic factor/leukemia inhibitory factor/gp 130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells. J. Neurosci. 21, 7642–7653.PubMedGoogle Scholar
  51. 51.
    Monville C., Coulpier M., Conti L., De Fraja C., Dreyfus P., Fages C., et al. (2001) Ciliary neurotrophic factor may activate mature astrocytes via binding with the leukemia inhibitory factor receptor. Mol. Cell. Neurosci. 17, 373–384.PubMedGoogle Scholar
  52. 52.
    Tropepe V., Hitoshi S., Sirard C., Mak T. W., Rossant J., and van der K.D. (2001) Direct neural fate specification from embryonic stem cells: a primitive mammalian neural stem cell stage acquired through a default mechanism. Neuron 30, 65–78.PubMedGoogle Scholar
  53. 53.
    Artavanis-Tsakonas S., Rand M. D., and Lake R. J. (1999) Notch signaling: cell fate control and signal integration in development. Science 284, 770–776.PubMedGoogle Scholar
  54. 54.
    Schroeter E. H., Kisslinger J. A., and Kopan R. (1998) Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393, 382–386.PubMedGoogle Scholar
  55. 55.
    Hitoshi S., Alexson T., Tropepe V., Donoviel D., Elia A. J., Nye J. S., et al. (2002) Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev. 16, 846–858.PubMedGoogle Scholar
  56. 56.
    Nakamura Y., Sakakibara S., Miyata T., Ogawa M., Shimazaki T., Weiss S., et al. (2000) The bHLH gene hes1 as a repressor of the neuronal commitment of CNS stem cells. J. Neurosci. 20, 283–293.PubMedGoogle Scholar
  57. 57.
    Ohtsuka T., Sakamoto M., Guillemot F., and Kageyama R. (2001) Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain. J. Biol. Chem. 276, 30,467–30,474.Google Scholar
  58. 58.
    Chambers C. B., Peng Y., Nguyen H., Gaiano N., Fishell G., and Nye J. S. (2001) Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors. Development 128, 689–702.PubMedGoogle Scholar
  59. 59.
    Solecki D. J., Liu X. L., Tomoda T., Fang Y., and Hatten M. E. (2001) Activated Notch2 signaling inhibits differentiation of cerebellar granule neuron precursors by maintaining proliferation. Neuron 31, 557–568.PubMedGoogle Scholar
  60. 60.
    Tanigaki K., Nogaki F., Takahashi J., Tashiro K., Kurooka H., and Honjo T. (2001) Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. Neuron 29, 45–55.PubMedGoogle Scholar
  61. 61.
    Furukawa T., Mukherjee S., Bao Z. Z., Morrow E. M., and Cepko C. L. (2000) rax, Hes1, and notch1 promote the formation of Muller glia by postnatal retinal progenitor cells. Neuron 26, 383–394.PubMedGoogle Scholar
  62. 62.
    Morrison S. J., Perez S. E., Qiao Z., Verdi J. M., Hicks C., Weinmaster G., et al. (2000) Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell 101, 499–510.PubMedGoogle Scholar
  63. 63.
    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
  64. 64.
    Fischer A. J. and Reh T. A. (2001) Muller glia are a potential source of neural regeneration in the postnatal chicken retina. Nat. Neurosci. 4, 247–252.PubMedGoogle Scholar
  65. 65.
    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.PubMedGoogle Scholar
  66. 66.
    Chenn A. and McConnell S. K. (1995) Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis. Cell 82, 631–641.PubMedGoogle Scholar
  67. 67.
    Heins N., Cremisi F., Malatesta P., Gangemi R. M., Corte G., Price J., et al. (2001) Emx2 promotes symmetric cell divisions and a multipotential fate in precursors from the cerebral cortex. Mol. Cell. Neurosci. 18, 485–502.PubMedGoogle Scholar
  68. 68.
    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.PubMedGoogle Scholar
  69. 69.
    Zhong W., Jiang M. M., Weinmaster G., Jan L. Y., and Jan Y. N. (1997) Differential expression of mammalian Numb, Numblike and Notch1 suggests distinct roles during mouse cortical neurogenesis. Development 124, 1887–1897.PubMedGoogle Scholar
  70. 70.
    Zhong W., Jiang M. M., Schonemann M. D., Meneses J. J., Pedersen R. A., Jan L. Y., et al. (2000) Mouse numb is an essential gene involved in cortical neurogenesis. Proc. Natl. Acad. Sci. USA 97, 6844–6849.PubMedGoogle Scholar
  71. 71.
    Imai T., Tokunaga A., Yoshida T., Hashimoto M., Mikoshiba K., Weinmaster G., et al. (2001) The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA. Mol. Cell. Biol. 21, 3888–3900.PubMedGoogle Scholar
  72. 72.
    Frise E., Knoblich J. A., Younger-Shepherd S., Jan L. Y., and Jan Y. N. (1996) The Drosophila Numb protein inhibits signaling of the Notch receptor during cell-cell interaction in sensory organ lineage. Proc. Natl. Acad. Sci. USA 93, 11,925–11,932.Google Scholar
  73. 73.
    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.PubMedGoogle Scholar
  74. 74.
    Kurata S., Go M. J., Artavanis-Tsakonas S., and Gehring W. J. (2000) Notch signaling and the determination of appendage identity. Proc. Natl. Acad. Sci. USA 97, 2117–2122.PubMedGoogle Scholar
  75. 75.
    Varnum-Finney B., Xu L., Brashem-Stein C., Nourigat C., Flowers D., Bakkour S., et al. (2000) Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat. Med. 6, 1278–1281.PubMedGoogle Scholar
  76. 76.
    Okano H., Imai T., and Okabe M. (2002) Musashi: a translational regulator of cell fate. J. Cell Sci. 115, 1355–1359.PubMedGoogle Scholar
  77. 77.
    Keyoung H. M., Roy N. S., Benraiss A., Louissaint A., Jr. Suzuki A., Hashimoto M., et al. (2001) High-yield selection and extraction of two promoter-defined phenotypes of neural stem cells from the fetal human brain. Nat. Biotechnol. 19, 843–850.PubMedGoogle Scholar
  78. 78.
    Sakakibara S. and Okano H. (1997) Expression of neural RNA-binding proteins in the postnatal CNS: implications of their roles in neuronal and glial cell development. J. Neurosci. 17, 8300–8312.PubMedGoogle Scholar
  79. 79.
    Sakakibara S., Nakamura Y., Satoh H., and Okano H. (2001) Rna-binding protein Musashi2: developmentally regulated expression in neural precursor cells and subpopulations of neurons in mammalian CNS. J. Neurosci. 21, 8091–8107.PubMedGoogle Scholar
  80. 80.
    Faux C. H., Turnley A. M., Epa R., Cappai R., and Bartiett P. F. (2001) Interactions between fibroblast growth factors and Notch regulate neuronal differentiation. J. Neurosci. 21, 5587–5596.PubMedGoogle Scholar
  81. 81.
    Anchan R. M., Reh T. A., Angello J., Balliet A., and Walker M. (1991) EGF and TGF-alpha stimulate retinal neuroepithelial cell proliferation in vitro. Neuron 6, 923–936.PubMedGoogle Scholar
  82. 82.
    Hynes M., Porter J. A., Chiang C., Chang D., Tessier-Lavigne M., Beachy P. A., et al. (1995) Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron 15, 35–44.PubMedGoogle Scholar
  83. 83.
    Marti E., Bumcrot D. A., Takada R., and McMahon A. P. (1995) Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature 375, 322–325.PubMedGoogle Scholar
  84. 84.
    Roelink H., Porter J. A., Chiang C., Tanabe Y., Chang D. T., Beachy P. A., et al. (1995) Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell 81, 445–455.PubMedGoogle Scholar
  85. 85.
    Wang M. Z., Jin P., Bumcrot D. A., Marigo V., McMahon A. P., Wang E. A., et al. (1995) Induction of dopaminergic neuron phenotype in the midbrain by Sonic hedgehog protein. Nat. Med. 1, 1184–1188.PubMedGoogle Scholar
  86. 86.
    Goodrich L. V., Milenkovic L., Higgins K. M., and Scott M. P. (1997) Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109–1113.PubMedGoogle Scholar
  87. 87.
    Raffel C., Jenkins R. B., Frederick L., Hebrink D., Alderete B., Fults D. W., et al. (1997) Sporadic medulloblastomas contain PTCH mutations. Cancer Res. 57, 842–845.PubMedGoogle Scholar
  88. 88.
    Vorechovsky I., Tingby O., Hartman M., Stromberg B., Nister M., Collins V. P., et al. (1997) Somatic mutations in the human homologue of Drosophila patched in primitive neuroectodermal tumours. Oncogene 15, 361–366.PubMedGoogle Scholar
  89. 89.
    Rowitch D. H., Jacques B., Lee S. M., Flax J. D., Snyder E. Y., and McMahon A. P. (1999) Sonic hedgehog regulates proliferation and inhibits differentiation of CNS precursor cells. J. Neurosci. 19, 8954–8965.PubMedGoogle Scholar
  90. 90.
    Jensen A. M. and Wallace V. A. (1997) Expression of Sonic hedgehog and its putative role as a precursor cell mitogen in the developing mouse retina. Development 124, 363–371.PubMedGoogle Scholar
  91. 91.
    Zhu G., Mehler M. F., Zhao J., Yu Y. S., and Kessler J. A. (1999) Sonic hedgehog and BMP2 exert opposing actions on proliferation and differentiation of embryonic neural progenitor cells. Dev. Biol. 215, 118–129.PubMedGoogle Scholar
  92. 92.
    Lee K. J. and Jessell T. M. (1999) The specification of dorsal cell fates in the vertebrate central nervous system. Annu. Rev. Neurosci. 22, 261–294.PubMedGoogle Scholar
  93. 93.
    Liem K. F., Jr. Tremml G., Roelink H., and Jessell T. M. (1995) Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm. Cell 82, 969–979.PubMedGoogle Scholar
  94. 94.
    Liem K. F., Jr. Tremml G., and Jessell T. M. (1997) A role for the roof plate and its resident TGFbeta-related proteins in neuronal patterning in the dorsal spinal cord. Cell 91, 127–138.PubMedGoogle Scholar
  95. 95.
    Powell P. P., Finklestein S. P., Dionne C. A., Jaye M., and Klagsbrun M. (1991) Temporal, differential and regional expression of mRNA for basic fibroblast growth factor in the developing and adult rat brain. Brain Res. Mol. Brain Res. 11, 71–77.PubMedGoogle Scholar
  96. 96.
    Raballo R., Rhee J., Lyn-Cook R., Leckman J. F., Schwartz M. L., and Vaccarino F. M. (2000) Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J. Neurosci. 20, 5012–5023.PubMedGoogle Scholar
  97. 97.
    Vaccarino F. M., Schwartz M. L., Raballo R., Nilsen J., Rhee J., Zhou M., et al. (1999) Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat. Neurosci. 2, 246–253.PubMedGoogle Scholar
  98. 98.
    Lim D. A., Tramontin A. D., Trevejo J. M., Herrera D. G., Garcia-Verdugo J. M., and Alvarez-Buylla A. (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713–726.PubMedGoogle Scholar
  99. 99.
    Morshead C. M., Reynolds B. A., Craig C. G., McBurney M. W., Staines W. A., Morassutti D., et al. (1994) Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13, 1071–1082.PubMedGoogle Scholar
  100. 100.
    Tropepe V., Craig C. G., Morshead C. M., and van der Kooy D. (1997) Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J. Neurosci. 17, 7850–7859.PubMedGoogle Scholar
  101. 101.
    Tessier-Lavigne M. and Goodman C. S. (1996) The molecular biology of axon guidance. Science 274, 1123–1133.PubMedGoogle Scholar
  102. 102.
    Drescher U. (1997) The Eph family in the patterning of neural development. Curr. Biol. 7, R799-R807.PubMedGoogle Scholar
  103. 103.
    O’Leary D. D. and Wilkinson D. G. (1999) Eph receptors and ephrins in neural development. Curr. Opin. Neurobiol. 9, 65–73.PubMedGoogle Scholar
  104. 104.
    Conover J. C., Doetsch F., Garcia-Verdugo J. M., Gale N. W., Yancopoulos G. D., and Alvarez-Buylla A. (2000) Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nat. Neurosci. 3, 1091–1097.Google Scholar
  105. 105.
    Brazel C. Y., Ducceschi M. H., Pytowski B., and Levison S. W. (2001) The FLT3 tyrosine kinase receptor inhibits neural stem/progenitor cell proliferation and collaborates with NGF to promote neuronal survival. Mol. Cell. Neurosci. 18, 381–393.PubMedGoogle Scholar
  106. 106.
    Wu J. P., Kuo J. S., Liu Y. L., and Tzeng S. F. (2000) Tumor necrosis factor-alpha modulates the proliferation of neural progenitors in the subventricular/ventricular zone of adult rat brain. Neurosci. Lett. 292, 203–206.PubMedGoogle Scholar
  107. 107.
    Nakatsuji Y. and Miller R. H. (2001) Selective cell-cycle arrest and induction of apoptosis in proliferating neural cells by ganglioside GM3. Exp. Neurol. 168, 290–299.PubMedGoogle Scholar
  108. 108.
    Gulisano M., Broccoli V., Pardini C., and Boncinelli E. (1996) Emx1 and Emx2 show different patterns of expression during proliferation and differentiation of the developing cerebral cortex in the mouse. Eur. J. Neurosci. 8, 1037–1050.PubMedGoogle Scholar
  109. 109.
    Mallamaci A., Iannone R., Briata P., Pintonello L., Mercurio S., Boncinelli E., et al. (1998) EMX2 protein in the developing mouse brain and olfactory area. Mech. Dev. 77, 165–172.PubMedGoogle Scholar
  110. 110.
    Simeone A., Gulisano M., Acampora D., Stornaiuolo A., Rambaldi M., and Boncinelli E. (1992) Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex. EMBO J. 11, 2541–2550.PubMedGoogle Scholar
  111. 111.
    Galli R., Fiocco R., De Filippis L., Muzio L., Gritti A., Mercurio S., et al. (2002) Emx2 regulates the proliferation of stem cells of the adult mammalian central nervous system. Development 129, 1633–1644.PubMedGoogle Scholar
  112. 112.
    Wood H. B. and Episkopou V. (1999) Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre- gastrulation to early somite stages. Mech. Dev. 86, 197–201.PubMedGoogle Scholar
  113. 113.
    Zappone M. V., Galli R., Catena R., Meani N., De Biasi S., Mattei E., et al. (2000) Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. Development 127, 2367–2382.PubMedGoogle Scholar
  114. 114.
    Seaberg R. M. and van der Kooy D. (2002) Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors. J. Neurosci. 22, 1784–1793.PubMedGoogle Scholar
  115. 115.
    Taupin P., Ray J., Fischer W. H., Suhr S. T., Hakansson K., Grubb A., et al. (2000) FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor. Neuron 28, 385–397.PubMedGoogle Scholar
  116. 116.
    Weiss S., Dunne C., Hewson J., Wohl C., Wheatley M., Peterson A. C., et al. (1996) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci. 16, 7599–7609.PubMedGoogle Scholar
  117. 117.
    Gehring W. J. (2002) The genetic control of eye development and its implications for the evolution of the various eye-types. Int. J. Dev. Biol. 46, 65–73.PubMedGoogle Scholar
  118. 118.
    Arsenijevic Y., Villemure J. G., Brunet J. F., Bloch J. J., Deglon N., Kostic C., et al. (2001) Isolation of multipotent neural precursors residing in the cortex of the adult human brain. Exp. Neurol. 170, 48–62.PubMedGoogle Scholar
  119. 119.
    Johansson C. B., Svensson M., Wallstedt L., Janson A. M., and Frisen J. (1999) Neural stem cells in the adult human brain. Exp. Cell Res. 253, 733–736.PubMedGoogle Scholar
  120. 120.
    Kukekov V. G., Laywell E. D., Suslov O., Davies K., Scheffler B., Thomas L. B., et al. (1999) Multipotent stem/progenitor cells with similar properties arise from two neurogenic regions of adult human brain. Exp. Neurol. 156, 333–344.PubMedGoogle Scholar
  121. 121.
    Pagano S. F., Impagnatiello F., Girelli M., Cova L., Grioni E., Onofri M., et al. (2000) Isolation and characterization of neural stem cells from the adult human olfactory bulb. Stem Cells 18, 295–300.PubMedGoogle Scholar
  122. 122.
    Palmer T. D., Schwartz P. H., Taupin P., Kaspar B., Stein S. A., and Gage F. H. (2001) Cell culture. Progenitor cells from human brain after death. Nature 411, 42–43.PubMedGoogle Scholar
  123. 123.
    Makarov V. L., Hirose Y., and Langmore J. P. (1997) Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 88, 657–666.PubMedGoogle Scholar
  124. 124.
    Greider C. W. and Blackburn E. H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405–413.PubMedGoogle Scholar
  125. 125.
    Greider C. W. and Blackburn E. H. (1987) The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell 51, 887–898.PubMedGoogle Scholar
  126. 126.
    Greider C. W. and Blackburn E. H. (1989) A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 337, 331–337.PubMedGoogle Scholar
  127. 127.
    Harley C. B., Futcher A. B., and Greider C. W. (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345, 458–460.PubMedGoogle Scholar
  128. 128.
    von Zglinicki T., Saretzki G., Docke W., and Lotze C. (1995) Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence? Exp. Cell Res. 220, 186–193.Google Scholar
  129. 129.
    Blasco M. A., Lee H. W., Hande M. P., Samper E., Lansdorp P. M., DePinho R. A., et al. (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34.PubMedGoogle Scholar
  130. 130.
    Hemann M. T., Strong M. A., Hao L. Y., and Greider C. W. (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107, 67–77.PubMedGoogle Scholar
  131. 131.
    Greider C. W. (1990) Telomeres, telomerase and senescence. Bioessays 12, 363–369.PubMedGoogle Scholar
  132. 132.
    Lundberg A. S., Hahn W. C., Gupta P., and Weinberg R. A. (2000) Genes involved in senescence and immortalization. Curr. Opin. Cell Biol. 12, 705–709.PubMedGoogle Scholar
  133. 133.
    Bodnar A. G., Ouellette M., Frolkis M., Holt S. E., Chiu C. P., Morin G. B., et al. (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349–352.PubMedGoogle Scholar
  134. 134.
    Wang J., Hannon G. J., and Beach D. H. (2000) Risky immortalization by telomerase. Nature 405, 755–756.PubMedGoogle Scholar
  135. 135.
    Fu W., Killen M., Culmsee C., Dhar S., Pandita T. K., and Mattson M. P. (2000) The catalytic subunit of telomerase is expressed in developing brain neurons and serves a cell survival-promoting function. J. Mol. Neurosci. 14, 3–15.PubMedGoogle Scholar
  136. 136.
    Klapper W., Shin T., and Mattson M. P. (2001) Differential regulation of telomerase activity and TERT expression during brain development in mice. J. Neurosci. Res. 64, 252–260.PubMedGoogle Scholar
  137. 137.
    Ostenfeld T., Caldwell M. A., Prowse K. R., Linskens M. H., Jauniaux E., and Svendsen C. N. (2000) Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation. Exp. Neurol. 164, 215–226.PubMedGoogle Scholar
  138. 138.
    Haik S., Gauthier L. R., Granotier C., Peyrin J. M., Lages C. S., Dormont D., et al. (2000) Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells. Oncogene 19, 2957–2966.PubMedGoogle Scholar
  139. 139.
    Boulaire J., Fotedar A., and Fotedar R. (2000) The functions of the cdk-cyclin kinase inhibitor p21WAF1. Pathol. Biol. (Paris), 48, 190–202.Google Scholar
  140. 140.
    Aloyz R. S., Bamji S. X., Pozniak C. D., Toma J. G., Atwal J., Kaplan D. R., et al. (1998) p53 is essential for developmental neuron death as regulated by the TrkA and p75 neurotrophin receptors. J. Cell Biol. 143, 1691–1703.PubMedGoogle Scholar
  141. 141.
    Serrano M., Lin A. W., McCurrach M. E., Beach D., and Lowe S. W. (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602.PubMedGoogle Scholar
  142. 142.
    Sherr C. J. and Weber J. D. (2000) The ARF/p53 pathway. Curr. Opin. Genet. Dev. 10, 94–99.PubMedGoogle Scholar
  143. 143.
    Allsopp R. C., Vaziri H., Patterson C., Goldstein S., Younglai E. V., Futche A. B., et al. (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc. Natl. Acad. Sci. USA 89, 10,114–10,118.Google Scholar
  144. 144.
    Vaziri H., Schachter F., Uchida I., Wei L., Zhu X., Effros R., et al. (1993) Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet. 52, 661–667.PubMedGoogle Scholar
  145. 145.
    Chen Q. and Ames B. N. (1994) Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells. Proc. Natl. Acad. Sci. USA 91, 4130–4134.PubMedGoogle Scholar
  146. 146.
    Saito H., Hammond A. T., and Moses R. E. (1995) The effect of low oxygen tension on the in vitro-replicative life span of human diploid fibroblast cells and their transformed derivatives. Exp. Cell Res. 217, 272–279.PubMedGoogle Scholar
  147. 147.
    Zhu J., Woods D., McMahon M., and Bishop J. M. (1998) Senescence of human fibroblasts induced by oncogenic. Raf. Genes Dev. 12, 2997–3007.Google Scholar
  148. 148.
    Lin A. W., Barradas M., Stone J. C., van Aelst L., Serrano M., and Lowe S. W. (1998) Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes Dev. 12, 3008–3019.PubMedGoogle Scholar
  149. 149.
    Leslie N. R. and Downes C. P. (2002) PTEN: The down side of PI 3-kinase signalling. Cell Signal. 14, 285–295.PubMedGoogle Scholar
  150. 150.
    Gimm O., Attie-Bitach T., Lees J. A., Vekemans M., and Eng C. (2000) Expression of the PTEN tumour suppressor protein during human development. Hum. Mol. Genet. 9, 1633–1639.PubMedGoogle Scholar
  151. 151.
    Luukko K., Ylikorkala A., Tiainen M., and Makela T. P. (1999) Expression of LKB1 and PTEN tumor suppressor genes during mouse embryonic development. Mech. Dev. 83, 187–190.PubMedGoogle Scholar
  152. 152.
    Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S. I., et al. (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943–1947.PubMedGoogle Scholar
  153. 153.
    Groszer M., Erickson R., Scripture-Adams D. D., Lesche R., Trumpp A., Zack J. A., et al. (2001) Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294, 2186–2189.PubMedGoogle Scholar
  154. 154.
    Frederiksen K., Jat P. S., Valtz N., Levy D., and McKay R. (1988) Immortalization of precursor cells from the mammalian CNS. Neuron 1, 439–448.PubMedGoogle Scholar
  155. 155.
    Renfranz P. J., Cunningham M. G., and McKay R. D. (1991) Region-specific differentiation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain. Cell 66, 713–729.PubMedGoogle Scholar
  156. 156.
    Lundberg C., Martinez-Serrano A., Cattaneo E., McKay R. D., and Bjorklund A. (1997) Survival, integration, and differentiation of neural stem cell lines after transplantation to the adult rat striatum. Exp. Neurol. 145, 342–360.PubMedGoogle Scholar
  157. 157.
    Villa A., Snyder E. Y., Vescovi A., and Martinez-Serrano A. (2000) Establishment and properties of a growth factor-dependent, perpetual neural stem cell line from the human CNS. Exp. Neurol. 161, 67–84.PubMedGoogle Scholar
  158. 158.
    Doetsch F., Verdugo J. M., Caille I., Alvarez-Buylla A., Chao M. V., and Casaccia-Bonnefil P. (2002) Lack of the cell-cycle inhibitor p27Kip1 results in selective increase of transit-amplifying cells for adult neurogenesis. J. Neurosci. 22, 2255–2264.PubMedGoogle Scholar
  159. 159.
    Dyer M. A. and Cepko C. L. (2001) Regulating proliferation during retinal development. Nat. Rev. Neurosci. 2, 333–342.PubMedGoogle Scholar
  160. 160.
    Dyer M. A. and Cepko C. L. (2000) p57 (Kip2) regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina. Development 127, 3593–3605.PubMedGoogle Scholar
  161. 161.
    Dyer M. A. and Cepko C. L. (2001) p27Kip1 and p57Kip2 regulate proliferation in distinct retinal progenitor cell populations. J. Neurosci. 21, 4259–4271.PubMedGoogle Scholar
  162. 162.
    Levine E. M., Close J., Fero M., Ostrovsky A., and Reh T. A. (2000) p27(Kip1) regulates cell cycle withdrawal of late multipotent progenitor cells in the mammalian retina. Dev. Biol. 219, 299–314.PubMedGoogle Scholar
  163. 163.
    Ohnuma S., Philpott A., Wang K., Holt C. E., and Harris W. A. (1999) p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina. Cell 99, 499–510.PubMedGoogle Scholar
  164. 164.
    Hoshimaru M., Ray J., Sah D. W., and Gage F. H. (1996) Differentiation of the immortalized adult neuronal progenitor cell line HC2S2 into neurons by regulatable suppression of the vmyc oncogene. Proc. Natl. Acad. Sci. USA 93, 1518–1523.PubMedGoogle Scholar
  165. 165.
    Synder E. Y., Deitcher D. L., Walsh C., Arnold-Aldea S., Hartwieg E. A., and Cepko C. L. (1992) Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell 68, 33–51.Google Scholar
  166. 166.
    Vlach J., Hennecke S., Alevizopoulos K., Conti D., and Amati B. (1996) Growth arrest by the cyclin-dependent kinase inhibitor p27Kip1 is abrogated by c-Myc. EMBO J. 15, 6595–6604.PubMedGoogle Scholar
  167. 167.
    Obaya A. J., Mateyak M. K., and Sedivy J. M. (1999) Mysterious liaisons: the relationship between c-Myc and the cell cycle. Oncogene 18, 2934–2941.PubMedGoogle Scholar
  168. 168.
    Perez-Roger I., Solomon D. L., Sewing A., and Land H. (1997) Myc activation of cyclin E/Cdk2 kinase involves induction of cyclin E gene transcription and inhibition of p27(Kip1) binding to newly formed complexes. Oncogene 14, 2373–2381.PubMedGoogle Scholar
  169. 169.
    Eisenman R. N. (2001) Deconstructing myc. Genes Dev. 15, 2023–2030.PubMedGoogle Scholar
  170. 170.
    Luscher B. (2001) Function and regulation of the transcription factors of the Myc/Max/Mad network. Gene 277, 1–14.PubMedGoogle Scholar
  171. 171.
    Zhou Z. Q. and Hurlin P. J. (2001) The interplay between Mad and Myc in proliferation and differentiation. Trends Cell Biol. 11, S10-S14.PubMedGoogle Scholar
  172. 172.
    Lee C. M. and Reddy E. P. (1999) The v-myc oncogene. Oncogene 18, 2997–3003.PubMedGoogle Scholar
  173. 173.
    Chisholm O., Stapleton P., and Symonds G. (1992) Constitutive expression of exogenous myc in myelomonocytic cells: acquisition of a more transformed phenotype and inhibition of differentiation induction. Oncogene 7, 1827–1836.PubMedGoogle Scholar
  174. 174.
    Pirami L., Stockinger B., Corradin S. B., Sironi M., Sassano M., Valsasnini P., et al. (1991) Mouse macrophage clones immortalized by retroviruses are functionally heterogeneous. Proc. Natl. Acad. Sci. USA 88, 7543–7547.PubMedGoogle Scholar
  175. 175.
    Ramsay G., Evan G. I., and Bishop J. M. (1984) The protein encoded by the human protooncogene c-myc. Proc. Natl. Acad. Sci. USA 81, 7742–7746.PubMedGoogle Scholar
  176. 176.
    MacAuley A. and Pawson T. (1988) Cooperative transforming activities of ras, myc, and src viral oncogenes in nonestablished rat adrenocortical cells. J. Virol. 62, 4712–4721.PubMedGoogle Scholar
  177. 177.
    Bechade C., Dambrine G., David-Pfeuty T., Esnault E., and Calothy G. (1988) Transformed and tumorigenic phenotypes induced by avian retroviruses containing the v-mil oncogene. J. Virol. 62, 1211–1218.PubMedGoogle Scholar
  178. 178.
    Wang J., Xie L. Y., Allan S., Beach D., and Hannon G. J. (1998) Myc activates telomerase. Genes Dev. 12, 1769–1774.PubMedGoogle Scholar
  179. 179.
    Flax J. D., Aurora S., Yang C., Simonin C., Wills A. M., Billinghurst L. L., et al. (1998) Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat. Biotechnol. 16, 1033–1039.PubMedGoogle Scholar
  180. 180.
    Li R., Thode S., Zhou J., Richard N., Pardinas J., Rao M. S., et al. (2000) Motoneuron differentiation of immortalized human spinal cord cell lines. J. Neurosci. Res. 59, 342–352.PubMedGoogle Scholar
  181. 181.
    Rubio F. J., Bueno C., Villa A., Navarro B., and Martinez-Serrano A. (2000) Genetically perpetuated human neural stem cells engraft and differentiate into the adult mammalian brain. Mol. Cell Neurosci. 16, 1–13.PubMedGoogle Scholar
  182. 182.
    Rosario C. M., Yandava B. D., Kosaras B., Zurakowski D., Sidman R. L., and Snyder E. Y. (1997) Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action. Development 124, 4213–4224.PubMedGoogle Scholar
  183. 183.
    Taylor R. M. and Snyder E. Y. (1997) Widespread engraftment of neural progenitor and stem-like cells throughout the mouse brain. Transplant. Proc. 29, 845–847.PubMedGoogle Scholar
  184. 184.
    Morshead C. M., Benveniste P., Iscove N. N., and van der K.D. (2002) Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nat. Med. 8, 268–273.PubMedGoogle Scholar
  185. 185.
    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.PubMedGoogle Scholar
  186. 186.
    Rideout W. M., III Eggan K., and Jaenisch R. (2001) Nuclear cloning and epigenetic reprogramming of the genome. Science 293, 1093–1098.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  1. 1.Unit of Oculogenetic, Department of Ophthalmology, Jules Gonin Eye HospitalLausanne University Medical SchoolSwitzerland

Personalised recommendations