Skip to main content

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

A unified hypothesis on the lineage of neural stem cells

Abstract

For many years, it was assumed that neurons and glia in the central nervous system were produced from two distinct precursor pools that diverged early during embryonic development. This theory was partially based on the idea that neurogenesis and gliogenesis occurred during different periods of development, and that neurogenesis ceased perinatally. However, there is now abundant evidence that neural stem cells persist in the adult brain and support ongoing neurogenesis in restricted regions of the central nervous system. Surprisingly, these stem cells have the characteristics of fully differentiated glia. Neuroepithelial stem cells in the embryonic neural tube do not show glial characteristics, raising questions about the putative lineage from embryonic to adult stem cells. In the developing brain, radial glia have long been known to produce cortical astrocytes, but recent data indicate that radial glia might also divide asymmetrically to produce cortical neurons. Here we review these new developments and propose that the stem cells in the central nervous system are contained within the neuroepithelial → radial glia → astrocyte lineage.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Classical and proposed stem-cell lineages.
Figure 2: Architecture and putative lineages in the adult subventricular zone.
Figure 3: Time-lapse videomicroscopy of radial glial-cell division.
Figure 4: Unified hypothesis for neural stem-cell development.
Figure 5: Oak versus pine-tree models of neural stem-cell lineages.

References

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

    CAS  PubMed  Google Scholar 

  2. Doetsch, F., Caille, I., Lim, D. A., García-Verdugo, J. M. & Alvarez-Buylla, A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 1–20 (1999).

    Google Scholar 

  3. Barres, B. A. A new role for glia: generation of neurons! Cell 97, 667–670 (1999).

    CAS  PubMed  Google Scholar 

  4. Lim, D. & Alvarez-Buylla, A. in Stem Cells and CNS Development (ed. Rao, M. S.) (Humana, Totowa, New Jersey, 2001 ).

    Google Scholar 

  5. Laywell, E. D., Rakic, P., Kukekov, V. G., Holland, E. C. & Steindler, D. A. Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc. Natl Acad. Sci. USA 97, 13883–13888 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Gaiano, N., Nye, J. S. & Fishell, G. Radial glial identity is promoted by notch1 signaling in the murine forebrain. Neuron 26, 395– 404 (2000).

    CAS  PubMed  Google Scholar 

  7. Malatesta, P., Hartfuss, E. & Gotz, M. Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127, 5253–5263 (2000).

    CAS  PubMed  Google Scholar 

  8. Noctor, S. C., Flint, A. C., Weissmann, T. A., Dammerman, R. S. & Kriegstein, A. R. Neurons derived from radial glial cells establish radial units in neocortex. Nature 109, 714–720 ( 2001).

    Google Scholar 

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

    Google Scholar 

  10. His, W. Die neuroblasten und deren entstehung im embryonalen mark. Abh. Kgl. Sachs. Ges. Wissensch. Math. Phys. Kl. 15, 311– 372 (1889).

    Google Scholar 

  11. Schaper, A. The earliest differentiation in the central nervous system of vertebrates . Science V, 430–431 (1987).

    Google Scholar 

  12. Sauer, F. C. Mitosis in the neural tube. J. Comp. Neurol. 62, 377–405 (1935).

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  14. Luskin, M. B., Pearlman, A. L. & Sanes, J. R. Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a recombinant retrovirus. Neuron 1, 635–647 ( 1988).

    CAS  PubMed  Google Scholar 

  15. Walsh, C. & Cepko, C. L. Clonally related cortical cells show several migration patterns. Science 241, 1342–1345 (1988).

    CAS  PubMed  Google Scholar 

  16. Temple, S. Division and differentiation of isolated CNS blast cells in microculture. Nature 340, 471–473 ( 1989).

    CAS  PubMed  Google Scholar 

  17. Gray, G. E. & Sanes, J. R. Lineage of radial glia in the chicken optic tectum. Development 114, 271– 283 (1992).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  19. Cepko, C. L. et al. Studies of cortical development using retrovirus vectors. Cold Spring Harb. Symp. Quant. Biol. LV, 265– 278 (1990).

    Google Scholar 

  20. Galileo, D. S., Gray, G. E., Owens, G. C., Majors, J. & Sanes, J. R. Neurons and glia arise from a common progenitor in chicken optic tectum: demonstration with two retroviruses and cell type-specific antibodies. Proc. Natl Acad. Sci. USA 87, 458–462 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Gray, G. E., Clover, J. C., Majors, J. & Sanes, J. R. Radial arrangement of clonally related cells in the chicken optic tectum: lineage analysis with a recombinant retrovirus. Proc. Natl Acad. Sci. USA 85, 7356–7360 ( 1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Goldman, S. A. Adult neurogenesis: from canaries to the clinic. J. Neurobiol. 36, 267–286 ( 1998).

    CAS  PubMed  Google Scholar 

  23. The Boulder Committee. Embryonic vertebrate central nervous system: revised terminology. Anat. Rec. 166 , 257–262 (1970).

  24. Altman, J. Are new neurons formed in the brains of adult mammals? Science 135, 1127–1128 ( 1962).

    CAS  PubMed  Google Scholar 

  25. Altman, J. Autoradiographic investigation of cell proliferation in the brains of rats and cats. Anat. Rec. 145, 573– 591 (1963).

    CAS  PubMed  Google Scholar 

  26. Altman, J. & Das, G. D. Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions. J. Comp. Neurol. 126, 337 –390 (1966).

    CAS  PubMed  Google Scholar 

  27. Altman, J. & Gopal, D. D. Post-natal origin of microneurons in the rat brain. Nature 207, 953– 956 (1965).

    CAS  PubMed  Google Scholar 

  28. Burd, G. D. & Nottebohm, F. Ultrastructural characterization of synaptic terminals formed on newly generated neurons in a song control nucleus of the adult canary forebrain. J. Comp. Neurol. 240, 143–152 (1985).

    CAS  PubMed  Google Scholar 

  29. Goldman, S. A. & Nottebohm, F. Neuronal production, migration & differentiation in a vocal control nucleus of the adult female canary brain. Proc. Natl Acad. Sci. USA 80, 2390–2394 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Alvarez-Buylla, A. & Lois, C. Neuronal stem cells in the brain of adult vertebrates. Stem Cells 13, 263–272 (1995).

    CAS  PubMed  Google Scholar 

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

    Google Scholar 

  32. Bayer, S. A. 3H-Thymidine-radiographic studies of neurogenesis in the rat olfactory bulb. Exp. Brain Res. 50, 329– 340 (1983).

    CAS  PubMed  Google Scholar 

  33. Penafiel, A., Gutierrez, A., Martin, R., Perez-Canellas, M. M. & De la Calle, A. A tangential neuronal migration in the olfactory bulbs of adult lizards. Neuroreport 7, 1257–1260 ( 1996).

    CAS  PubMed  Google Scholar 

  34. Trice, J. E. & Stanfield, B. B. Evidence for the generation in the adult rat dentate gyrus of neurons that extend axonal projections. Ann. Neurol. 20, 392 (1986).

    Google Scholar 

  35. Alvarez-Buylla, A., Ling, C.-Y. & Yu, W. S. Contribution of neurons born during embryonic, juvenile and adult life to the brain of adult canaries: Regional specificity and delayed birth of neurons in the song-control nuclei. J. Comp. Neurol. 347, 233–248 (1994).

    CAS  PubMed  Google Scholar 

  36. Alvarez-Buylla, A., Theelen, M. & Nottebohm, F. Birth of projection neurons in the higher vocal center of the canary forebrain before, during & after song learning. Proc. Natl Acad. Sci. USA 85, 8722– 8726 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Scharff, C., Kirn, J. R., Grossman, M., Macklis, J. D. & Nottebohm, F. Targeted neuronal death affects neuronal replacement and vocal behavior in adult songbirds. Neuron 25, 481–492 ( 2000).

    CAS  PubMed  Google Scholar 

  38. Rakic, P. Limits of neurogenesis in primates. Science 227, 1054–1056 (1985).

    CAS  PubMed  Google Scholar 

  39. Kaplan, M. & Bell, D. Mitotic neuroblasts in the 9 day old and 11 month old rodent hippocampus. J. Neurosci. 4 , 1429–1441 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Cameron, H. A., Wooley, C. S., McEwen, B. S. & Gould, E. Differentiation of newly born neuron and glia in the dentate gyrus of the adult rat. Neuroscience 56, 337– 344 (1993).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  43. Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A. M. & Fuchs, E. Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J. Neurosci. 17, 2492– 2498 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Doetsch, F. & Alvarez-Buylla, A. Network of tangential pathways for neuronal migration in adult mammalian brain. Proc. Natl Acad. Sci. USA 93, 14895–14900 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Eriksson, P. S. et al. Neurogenesis in the adult human hippocampus. Nature Med. 4, 1313–1317 ( 1998).

    CAS  PubMed  Google Scholar 

  46. Lewis, P. D. Mitotic activity in the primate subependymal layer and the genesis of gliomas . Nature 217, 974–975 (1968).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  48. Huang, L., DeVries, G. J. & Bittman, E. L. Photoperiod regulates neuronal bromodeoxyuridine labeling in the brain of a seasonally breeding mammal. J. Neurobiol. 36, 410–420 ( 1998).

    CAS  PubMed  Google Scholar 

  49. Blakemore, W. F. & Jolly, D. R. The subependymal plate and associated ependyma in the dog. An ultrastructural study. J. Neurocytol. 1, 69–84 (1972).

    CAS  PubMed  Google Scholar 

  50. McDermott, K. W. G. & Lantos, P. L. Cell proliferation in the subependymal layer of the postnatal marmoset, Callithrix jacchus . Dev. Brain Res. 57, 269– 277 (1990).

    CAS  Google Scholar 

  51. Goldman, S. A., Kirschenbaum, B., Harrison-Restelli, C. & Thaler, H. T. Neuronal precursors of the adult rat subependymal zone persist into senescence, with no decline in spatial extent or response to BDNF. J. Neurobiol. 32, 554–566 ( 1997).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Luskin, M. B. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11, 173–189 (1993).

    CAS  PubMed  Google Scholar 

  54. Lois, C. & Alvarez-Buylla, A. Long-distance neuronal migration in the adult mammalian brain. Science 264, 1145–1148 (1994).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Lois, C., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Chain migration of neuronal precursors . Science 271, 978–981 (1996).

    CAS  PubMed  Google Scholar 

  57. Wichterle, H., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Direct evidence for homotypic, glia-independent neuronal migration. Neuron 18, 779– 791 (1997).

    CAS  PubMed  Google Scholar 

  58. Lim, D. A. et al. Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713– 726 (2000).

    CAS  PubMed  Google Scholar 

  59. Reynolds, B. & Weiss, S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707–1710 ( 1992).

    CAS  PubMed  Google Scholar 

  60. Morshead, C. M. et al. Neural stem cells in the adult mammalian forebrain: A relatively quiescent subpopulation of subependymal cells. Neuron 13, 1071–1082 (1994).

    CAS  PubMed  Google Scholar 

  61. Gage, F. H., Ray, J. & Fisher, L. J. Isolation, characterization & use of stem cells from the CNS. Annu. Rev. Neurosci. 18, 159– 192 (1995).

    CAS  PubMed  Google Scholar 

  62. Weiss, S. et al. Is there a neural stem cell in the mammalian forebrain? Trends Neurosci. 19, 387–393 (1996).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  65. Gage, F. H. Discussion point: stem cells of the central nervous system. Curr. Opin. Neurobiol. 8, 671–675 (1998).

    CAS  PubMed  Google Scholar 

  66. Alvarez-Buylla, A. & Temple, S. Stem cells in the developing and adult nervous system. J. Neurobiol. 36, 105–110 (1998).

    CAS  PubMed  Google Scholar 

  67. Coulombe, P. A., Kopan, R. & Fuchs, E. Expression of keratin K14 in the epidermis and hair follicle: insights into complex programs of differentiation. J. Cell Biol. 109, 2295–2312 ( 1989).

    CAS  PubMed  Google Scholar 

  68. Vasioukhin, V., Degenstein, L., Wise, B. & Fuchs, E. The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin. Proc. Natl Acad. Sci. USA 96, 8551–8556 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  71. Johansson, C. B. et al. Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96, 25– 34 (1999).

    CAS  PubMed  Google Scholar 

  72. Chiasson, B. J., Tropepe, V., Morshead, C. M. & Van der Kooy, D. Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics . J. Neurosci. 19, 4462– 4471 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Doetsch, F., García-Verdugo, J. M. & Alvarez-Buylla, A. Regeneration of a germinal layer in the adult mammalian brain. Proc. Natl Acad. Sci. USA 96 , 11619–11624 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Holland, E. C. & Varmus, H. E. Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice. Proc. Natl Acad. Sci. USA 95 , 1218–1223 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  77. Sotelo, J. R. & Trujillo-Cenóz, O. Electron microscope study on the development of ciliary components of the neural epithelium of the chick embryo. Z. Zellforsch. 49, 1– 12 (1958).

    CAS  PubMed  Google Scholar 

  78. Stensaas, L. J. & Stensaas, S. S. An electron microscope study of cells in the matrix and intermediate laminae of the cerebral hemisphere of the 45mm rabbit embryo. Z. Zellforsch. 91, 341–365 (1968).

    CAS  PubMed  Google Scholar 

  79. Cohen, E. & Meininger, V. Ultrastructural analysis of primary cilium in the embryonic nervous tissue of mouse. Int. J. Dev. Neurosci. 5, 43–51 (1987 ).

    CAS  PubMed  Google Scholar 

  80. Magini, G. Nouvelles recherches histologiques sur le cerveau du foetus. Arch. Ital. Biol. 10, 384–387 (1888).

    Google Scholar 

  81. Schmechel, D. E. & Rakic, P. A Golgi study of radial glia cells in developing monkey telencephalon: morphogenesis and transformation into astrocytes. Anat. Embryol. 156, 115 –152 (1979).

    CAS  Google Scholar 

  82. Gadisseux, J. F., Evrard, P., Misson, J. P. & Caviness, V. S. Dynamic structure of the radial glial fiber system of the developing murine cerebral wall. An immunocytochemical analysis. Dev. Brain Res. 50, 55–67 ( 1989).

    CAS  Google Scholar 

  83. Rakic, P. Mode of cell migration to the superficial layers of fetal monkey neocortex . J. Comp. Neurol. 145, 61– 84 (1972).

    CAS  PubMed  Google Scholar 

  84. Ramón y Cajal, S. Histologie du Système Nerveux de l'Homme et des Vertébrés (Maloine, Paris, 1911).

    Google Scholar 

  85. Levitt, P. R., Cooper, M. L. & Rakic, P. Coexistence of neuronal and glial precursor cells in the cerebral ventricular zone of the fetal monkey: an ultrastructural immunoperoxidase analysis. J. Neurosci. 1, 27– 39 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Pixley, S. K. R. & De Vellis, J. Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Dev. Brain Res. 15, 201– 209 (1984).

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  88. Hockfield, S. & McKay, R. D. G. Identification of major cell classes in the developing mammalian nervous system. J. Neurosci. 5, 3310–3328 ( 1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Misson, J. P., Edwards, M. A., Yamamoto, M. & Caviness, V. S. Jr Mitotic cycling of radial glial cells of the fetal murine cerebral wall: a combined autoradiographic and immunohistochemical study. Dev. Brain Res. 38, 183– 190 (1988).

    Google Scholar 

  90. Frederiksen, K. & McKay, R. D. G. Proliferation and differentiation of rat neuroepithelial precursor cells in vivo. J. Neurosci. 8, 1144–1151 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. McKay, R. D. G. The origins of cellular diversity in the mammalian central nervous system . Cell 58, 815–821 (1989).

    CAS  PubMed  Google Scholar 

  92. Alvarez-Buylla, A., García-Verdugo, J. M., Mateo, A. & Merchant-Larios, H. Primary neural precursors and intermitotic nuclear migration in the ventricular zone of adult canaries. J. Neurosci. 18, 1020–1037 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Horstmann, E. Die faserglia des selachiergehirns. Z. Zellforsch. 39, 588–617 (1954).

    CAS  PubMed  Google Scholar 

  94. Stensaas, L. J. & Stensass, S. S. Light microscopy of glial cells in turtles and birds. Z. Zellforsch. 91, 315–340 (1968).

    CAS  PubMed  Google Scholar 

  95. Stevenson, J. A. & Yoon, M. G. Morphology of radial glia, ependymal cells and periventricular neurons in the optic tectum of goldfish (Carassius auratus). J. Comp. Neurol. 205, 128–138 (1982).

    CAS  PubMed  Google Scholar 

  96. Connors, B. W. & Ransom, B. R. Electrophysiological properties of ependymal cells (radial glia) in dorsal cortex of the turtle, Pseudemys scripta. J. Physiol. 385, 287–306 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Zamora, A. J. & Mutin, M. Vimentin and glial fibrillary acidic protein filaments in radial glia of the adult urodele spinal cord. Neuroscience 27, 279–288 (1988).

    CAS  PubMed  Google Scholar 

  98. Alvarez-Buylla, A., Theelen, M. & Nottebohm, F. Mapping of radial glia and of a new cell type in adult canary brain. J. Neurosci. 8, 2707– 2712 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Alvarez-Buylla, A., Theelen, M. & Nottebohm, F. Proliferation 'hot spots' in adult avian ventricular zone reveal radial cell division. Neuron 5, 101–109 (1990).

    CAS  PubMed  Google Scholar 

  100. Goldman, J. E. Lineage, migration and fate determination of postnatal subventricular zone cells in the mammalian CNS. J. Neurooncol. 24, 61–64 (1995).

    CAS  PubMed  Google Scholar 

  101. Smart, I. H. M. Cortical histogenesis and the 'glial coordinate system' of Nieuwenhuys. J. Anat. 121, 71–84 ( 1978).

    Google Scholar 

  102. Rakic, P. Specification of cerebral cortical areas. Science 241 , 170–176 (1988).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  104. McConnell, S. K. Constructing the cerebral cortex: neurogenesis and fate determination. Neuron 15, 761–768 ( 1995).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Supported in part by NIH grants to A.A.-B. A.D.T. is supported by a fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation.

Author information

Authors and Affiliations

Authors

Related links

Related links

DATABASE LINKS

EGF

bFGF

GFAP

nestin

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Alvarez-Buylla, A., García-Verdugo, J. & Tramontin, A. A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2, 287–293 (2001). https://doi.org/10.1038/35067582

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35067582

Further reading

Search

Quick links

Nature Briefing

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

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