Neural Stem Cells

  • Yoko Arai
  • Wieland B. Huttner
  • Federico Calegari
Chapter

Abstract

Neural stem cells are the source of all neurons, astrocytes and oligodendrocytes of the central nervous system. While the vast majority of neural stem cells are consumed during embryonic development, a subpopulation persists in specialized regions of the adult mammalian brain where addition of cells, notably neurons, ­continues throughout life. The significance and physiological role of adult neurogenesis are still debated but it is generally believed that neural stem cells may be used to establish novel therapies for certain neural pathologies. In this chapter we describe the main features of neural stem cells during embryonic development and adulthood as well as the key mechanisms known to influence their proliferation versus differentiation. We then discuss the current views on the function of adult neurogenesis and the first attempts to use neural stem cells in therapy. Since the focus of this book is on regenerative medicine, we will mainly describe neural stem cells of mammalian organisms and briefly mention studies on other phyla only if particularly relevant.

Keywords

Neural Stem Cell Neural Progenitor Ependymal Cell Adult Neurogenesis Ventricular Zone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AP

anterior-posterior

AraC

arabinosyde-C

bHLH

basic helix-loop-helix

BMP

bone morphogenic protein

BrdU

bromodeoxyuridine

CDK

cyclin-dependent kinase

CNS

central nervous system

CSL

CBF1/RBPJk/Supplessor of hairless/Lag1

Dnmts

DNA methyltransferases

DV

dorso-ventral

EGF

epidermal growth factor

FGF2

fibroblast growth factor 2

γGABA

γ-aminobutyric acid

HATs

histone acetylases

HDACs

histone deacetylases

HIF-Ia

hypoxia-inducible factor Iα

INM

interkinetic nuclear migration

miRNAs

microRNAs

Ngn

neurogenin

NICD

notch receptor

NSC

neural stem cells

RA

retinoic acid

SGZ

subgranular zone

Shh

sonic hedgehog

SVZ

sub-ventricular zone

VZ

ventricular zone

References

  1. Abrous, D. N., Koehl, M., Le Moal, M., 2005. Adult neurogenesis: from precursors to network and physiology. Physiol Rev. 85, 523–69.PubMedGoogle Scholar
  2. Ackman, J. B., Siddiqi, F., Walikonis, R. S., LoTurco, J. J., 2006. Fusion of microglia with pyramidal neurons after retroviral infection. J Neurosci. 26, 11413–22.PubMedGoogle Scholar
  3. Ahn, S., Joyner, A. L., 2005. In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog. Nature. 437, 894–7.PubMedGoogle Scholar
  4. Aigner, S., Denli, A. M., Gage, F. H., 2007. A novel model for an older remodeler: the BAF swap in neurogenesis. Neuron. 55, 171–3.PubMedGoogle Scholar
  5. Alcantara Llaguno, S., Chen, J., Kwon, C. H., Jackson, E. L., Li, Y., Burns, D. K., Alvarez-Buylla, A., Parada, L. F., 2009. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell. 15, 45–56.PubMedGoogle Scholar
  6. Alonso, M., Viollet, C., Gabellec, M. M., Meas-Yedid, V., Olivo-Marin, J. C., Lledo, P. M., 2006. Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb. J Neurosci. 26, 10508–13.PubMedGoogle Scholar
  7. Altman, J., 1962. Are new neurons formed in the brains of adult mammals? Science. 135, 1127–8.PubMedGoogle Scholar
  8. Alvarez-Buylla, A., Lim, D. A., 2004. For the long run: maintaining germinal niches in the adult brain. Neuron. 41, 683–6.PubMedGoogle Scholar
  9. Ambros, V., 2004. The functions of animal microRNAs. Nature. 431, 350–5.PubMedGoogle Scholar
  10. Androutsellis-Theotokis, A., Leker, R. R., Soldner, F., Hoeppner, D. J., Ravin, R., Poser, S. W., Rueger, M. A., Bae, S. K., Kittappa, R., McKay, R. D., 2006. Notch signalling regulates stem cell numbers in vitro and in vivo. Nature. 442, 823–6.PubMedGoogle Scholar
  11. Arai, Y., Funatsu, N., Numayama-Tsuruta, K., Nomura, T., Nakamura, S., Osumi, N., 2005. Role of Fabp7, a downstream gene of Pax6, in the maintenance of neuroepithelial cells during early embryonic development of the rat cortex. J Neurosci. 25, 9752–61.PubMedGoogle Scholar
  12. Arias-Carrion, O., Yuan, T. F., 2009. Autologous neural stem cell transplantation: A new treatment option for Parkinson’s disease? Med Hypotheses.73, 757–9PubMedGoogle Scholar
  13. Artavanis-Tsakonas, S., Rand, M. D., Lake, R. J., 1999. Notch signaling: cell fate control and signal integration in development. Science. 284, 770–6.PubMedGoogle Scholar
  14. Attardo, A., Calegari, F., Haubensak, W., Wilsch-Bräuninger, M., Huttner, W. B., 2008. Live imaging at the onset of cortical neurogenesis reveals differential appearance of the neuronal phenotype in apical versus basal progenitor progeny. PLoS ONE. 3, e2388.PubMedGoogle Scholar
  15. Barry, D., McDermott, K., 2005. Differentiation of radial glia from radial precursor cells and transformation into astrocytes in the developing rat spinal cord. Glia. 50, 187–97.PubMedGoogle Scholar
  16. Bartel, D. P., 2009. MicroRNAs: target recognition and regulatory functions. Cell. 136, 215–33.PubMedGoogle Scholar
  17. Bautch, V. L., James, J. M., 2009. Neurovascular development: the beginning of a beautiful friendship. Cell Adh Migr. 3, 199–204.PubMedGoogle Scholar
  18. Bernstein, E., Kim, S. Y., Carmell, M. A., Murchison, E. P., Alcorn, H., Li, M. Z., Mills, A. A., Elledge, S. J., Anderson, K. V., Hannon, G. J., 2003. Dicer is essential for mouse development. Nat Genet. 35, 215–7.PubMedGoogle Scholar
  19. Biron, V. L., McManus, K. J., Hu, N., Hendzel, M. J., Underhill, D. A., 2004. Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development. Dev Biol. 276, 337–51.PubMedGoogle Scholar
  20. Borello, U., Cobos, I., Long, J. E., McWhirter, J. R., Murre, C., Rubenstein, J. L., 2008. FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development. Neural development. 3, 17.PubMedGoogle Scholar
  21. BoulderComm., 1970. Embryonic vertebrate central nervous system: revised terminology. The Boulder Committee. Anat Rec. 166, 257–61.Google Scholar
  22. Breunig, J. J., Arellano, J. I., Macklis, J. D., Rakic, P., 2007a. Everything that glitters isn’t gold: a critical review of postnatal neural precursor analyses. Cell Stem Cell. 1, 612–27.PubMedGoogle Scholar
  23. Breunig, J. J., Sarkisian, M. R., Arellano, J. I., Morozov, Y. M., Ayoub, A. E., Sojitra, S., Wang, B., Flavell, R. A., Rakic, P., Town, T., 2008. Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling. Proc Natl Acad Sci USA. 105, 13127–32.PubMedGoogle Scholar
  24. Breunig, J. J., Silbereis, J., Vaccarino, F. M., Sestan, N., Rakic, P., 2007b. Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus. Proc Natl Acad Sci USA. 104, 20558–63.PubMedGoogle Scholar
  25. Brinton, R. D., Wang, J. M., 2006. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer’s disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 3, 185–90.PubMedGoogle Scholar
  26. Briscoe, J., Pierani, A., Jessell, T. M., Ericson, J., 2000. A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell. 101, 435–45.PubMedGoogle Scholar
  27. Calegari, F., Haubensak, W., Haffner, C., Huttner, W. B., 2005. Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development. J Neurosci. 25, 6533–8.PubMedGoogle Scholar
  28. Cameron, H. A., McKay, R. D., 2001. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol. 435, 406–17.PubMedGoogle Scholar
  29. Cao, L., Jiao, X., Zuzga, D. S., Liu, Y., Fong, D. M., Young, D., During, M. J., 2004. VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet. 36, 827–35.PubMedGoogle Scholar
  30. Cao, X., Pfaff, S. L., Gage, F. H., 2007. A functional study of miR-124 in the developing neural tube. Genes Dev. 21, 531–6.PubMedGoogle Scholar
  31. Cao, X., Yeo, G., Muotri, A. R., Kuwabara, T., Gage, F. H., 2006. Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci. 29, 77–103.PubMedGoogle Scholar
  32. Capela, A., Temple, S., 2002. LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron. 35, 865–75.PubMedGoogle Scholar
  33. Carlen, M., Meletis, K., Goritz, C., Darsalia, V., Evergren, E., Tanigaki, K., Amendola, M., Barnabe-Heider, F., Yeung, M. S., Naldini, L., Honjo, T., Kokaia, Z., Shupliakov, O., Cassidy, R. M., Lindvall, O., Frisen, J., 2009. Forebrain ependymal cells are notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci. 12, 259–67.PubMedGoogle Scholar
  34. Castro, D. S., Skowronska-Krawczyk, D., Armant, O., Donaldson, I. J., Parras, C., Hunt, C., Critchley, J. A., Nguyen, L., Gossler, A., Göttgens, B., Matter, J. M., Guillemot, F., 2006. Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif. Dev Cell. 11, 831–44.PubMedGoogle Scholar
  35. Caviness, V. S., Takahashi, T., Nowakowski, R. S., 1995. Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model. Trends Neurosci. 18, 379–83.PubMedGoogle Scholar
  36. Cayuso, J., Martí, E., 2005. Morphogens in motion: growth control of the neural tube. J Neurobiol. 64, 376–87.PubMedGoogle Scholar
  37. Cayuso, J., Ulloa, F., Cox, B., Briscoe, J., Martí, E., 2006. The Sonic hedgehog pathway independently controls the patterning, proliferation and survival of neuroepithelial cells by regulating Gli activity. Development. 133, 517–28.PubMedGoogle Scholar
  38. Cheng, L. C., Pastrana, E., Tavazoie, M., Doetsch, F., 2009. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci. 12, 399–408.PubMedGoogle Scholar
  39. Cheng, L. C., Tavazoie, M., Doetsch, F., 2005. Stem cells: from epigenetics to microRNAs. Neuron. 46, 363–7.PubMedGoogle Scholar
  40. Chenn, A., McConnell, S. K., 1995. Cleavage orientation and the asymmetric inheritance of notch1 immunoreactivity in mammalian neurogenesis. Cell. 82, 631–41.PubMedGoogle Scholar
  41. Chenn, A., Walsh, C. A., 2003. Increased neuronal production, enlarged forebrains and cytoarchitectural distortions in beta-catenin overexpressing transgenic mice. Cereb Cortex. 13, 599–606.PubMedGoogle Scholar
  42. Chesnutt, C., Burrus, L. W., Brown, A. M., Niswander, L., 2004. Coordinate regulation of neural tube patterning and proliferation by TGFbeta and WNT activity. Dev Biol. 274, 334–47.PubMedGoogle Scholar
  43. Chiang, C., Litingtung, Y., Lee, E., Young, K. E., Corden, J. L., Westphal, H., Beachy, P. A., 1996. Cyclopia and defective axial patterning in mice lacking sonic hedgehog gene function. Nature. 383, 407–13.PubMedGoogle Scholar
  44. Chiasson, B. J., Tropepe, V., Morshead, C. M., 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, 4462–71.PubMedGoogle Scholar
  45. Chojnacki, A. K., Mak, G. K., Weiss, S., 2009. Identity crisis for adult periventricular neural stem cells: subventricular zone astrocytes, ependymal cells or both? Nat Rev Neurosci. 10, 153–63.PubMedGoogle Scholar
  46. Colleoni, F., Torrente, Y., 2008. The new challenge of stem cell: brain tumour therapy. Cancer Lett. 272, 1–11.PubMedGoogle Scholar
  47. Curtis, M. A., Kam, M., Nannmark, U., Anderson, M. F., Axell, M. Z., Wikkelso, C., Holtas, S., van Roon-Mom, W. M., Bjork-Eriksson, T., Nordborg, C., Frisen, J., Dragunow, M., Faull, R. L., Eriksson, P. S., 2007. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science. 315, 1243–9.PubMedGoogle Scholar
  48. Dahmane, N., Sánchez, P., Gitton, Y., Palma, V., Sun, T., Beyna, M., Weiner, H., Ruiz i Altaba, A., 2001. The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development. 128, 5201–12.PubMedGoogle Scholar
  49. Dayer, A. G., Cleaver, K. M., Abouantoun, T., Cameron, H. A., 2005. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol. 168, 415–27.PubMedGoogle Scholar
  50. De Pietri Tonelli, D., Pulvers, J. N., Haffner, C., Murchison, E. P., Hannon, G. J., Huttner, W. B., 2008. miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex. Development. 135, 3911–21.PubMedGoogle Scholar
  51. Dehay, C., Kennedy, H., 2007. Cell-cycle control and cortical development. Nat Rev Neurosci. 8, 438–50.PubMedGoogle Scholar
  52. Deng, W., Aimone, J. B., Gage, F. H., 2010. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci. 11, 339–50.PubMedGoogle Scholar
  53. Dickinson, M. E., Krumlauf, R., McMahon, A. P., 1994. Evidence for a mitogenic effect of Wnt-1 in the developing mammalian central nervous system. Development. 120, 1453–71.PubMedGoogle Scholar
  54. Diez del Corral, R., Breitkreuz, D. N., Storey, K. G., 2002. Onset of neuronal differentiation is regulated by paraxial mesoderm and requires attenuation of FGF signalling. Development. 129, 1681–91.PubMedGoogle Scholar
  55. Diez del Corral, R., Olivera-Martinez, I., Goriely, A., Gale, E., Maden, M., Storey, K., 2003. Opposing FGF and retinoid pathways control ventral neural pattern, neuronal differentiation, and segmentation during body axis extension. Neuron. 40, 65–79.PubMedGoogle Scholar
  56. Doe, C. Q., Skeath, J. B., 1996. Neurogenesis in the insect central nervous system. Curr Opin Neurobiol. 6, 18–24.PubMedGoogle Scholar
  57. Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M., Alvarez-Buylla, A., 1999a. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 97, 703–16.PubMedGoogle Scholar
  58. Doetsch, F., Garcia-Verdugo, J. M., Alvarez-Buylla, A., 1997. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci. 17, 5046–61.PubMedGoogle Scholar
  59. Doetsch, F., Garcia-Verdugo, J. M., Alvarez-Buylla, A., 1999b. Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci U S A. 96, 11619–24.PubMedGoogle Scholar
  60. Du, T., Zamore, P. D., 2005. MicroPrimer: the biogenesis and function of microRNA. Development. 132, 4645–52.PubMedGoogle Scholar
  61. Ekholm, S. V., Reed, S. I., 2000. Regulation of G(1) cyclin-dependent kinases in the mammalian cell cycle. Curr Opin Cell Biol. 12, 676–84.PubMedGoogle Scholar
  62. Erecińska, M., Silver, I. A., 2001. Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol. 128, 263–76.PubMedGoogle Scholar
  63. Eriksson, P. S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., Gage, F. H., 1998. Neurogenesis in the adult human hippocampus. Nat Med. 4, 1313–7.PubMedGoogle Scholar
  64. Estivill-Torrus, G., Pearson, H., van Heyningen, V., Price, D. J., Rashbass, P., 2002. Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors. Development. 129, 455–66.PubMedGoogle Scholar
  65. Ever, L., Gaiano, N., 2005. Radial ‘glial’ progenitors: neurogenesis and signaling. Curr Opin Neurobiol. 15, 29–33.PubMedGoogle Scholar
  66. Fabel, K., Tam, B., Kaufer, D., Baiker, A., Simmons, N., Kuo, C. J., Palmer, T. D., 2003. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci. 18, 2803–12.PubMedGoogle Scholar
  67. Fan, G., Martinowich, K., Chin, M. H., He, F., Fouse, S. D., Hutnick, L., Hattori, D., Ge, W., Shen, Y., Wu, H., ten Hoeve, J., Shuai, K., Sun, Y. E., 2005. DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development. 132, 3345–56.PubMedGoogle Scholar
  68. Farkas, L. M., Huttner, W. B., 2008. The cell biology of neural stem and progenitor cells and its significance for their proliferation versus differentiation during mammalian brain development. Curr Opin Cell Biol. 20, 707–15.PubMedGoogle Scholar
  69. Filippov, V., Kronenberg, G., Pivneva, T., Reuter, K., Steiner, B., Wang, L. P., Yamaguchi, M., Kettenmann, H., Kempermann, G., 2003. Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Mol Cell Neurosci. 23, 373–82.PubMedGoogle Scholar
  70. Firket, H., Verly, W. G., 1958. Autoradiographic visualization of synthesis of deoxyribonucleic acid in tissue culture with tritium-labelled thymidine. Nature. 181, 274–5.PubMedGoogle Scholar
  71. Fish, J. L., Dehay, C., Kennedy, H., Huttner, W. B., 2008. Making bigger brains-the evolution of neural-progenitor-cell division. J Cell Sci. 121, 2783–93.PubMedGoogle Scholar
  72. Fish, J. L., Kosodo, Y., Enard, W., Pääbo, S., Huttner, W. B., 2006. Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc Natl Acad Sci USA. 103, 10438–43.PubMedGoogle Scholar
  73. Fode, C., Ma, Q., Casarosa, S., Ang, S. L., Anderson, D. J., Guillemot, F., 2000. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev. 14, 67–80.PubMedGoogle Scholar
  74. Frielingsdorf, H., Schwarz, K., Brundin, P., Mohapel, P., 2004. No evidence for new dopaminergic neurons in the adult mammalian substantia nigra. Proc Natl Acad Sci USA. 101, 10177–82.PubMedGoogle Scholar
  75. Fukuda, S., Kato, F., Tozuka, Y., Yamaguchi, M., Miyamoto, Y., Hisatsune, T., 2003. Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus. J Neurosci. 23, 9357–66.PubMedGoogle Scholar
  76. Gavin, B. J., McMahon, J. A., McMahon, A. P., 1990. Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development. Genes Dev. 4, 2319–32.PubMedGoogle Scholar
  77. Gerdes, J. M., Davis, E. E., Katsanis, N., 2009. The vertebrate primary cilium in development, homeostasis, and disease. Cell. 137, 32–45.PubMedGoogle Scholar
  78. Givogri, M. I., de Planell, M., Galbiati, F., Superchi, D., Gritti, A., Vescovi, A., de Vellis, J., Bongarzone, E. R., 2006. Notch signaling in astrocytes and neuroblasts of the adult subventricular zone in health and after cortical injury. Dev Neurosci. 28, 81–91.PubMedGoogle Scholar
  79. Götz, M., Huttner, W. B., 2005. The cell biology of neurogenesis. Nat Rev Mol Cell Biol. 6, 777–88.PubMedGoogle Scholar
  80. Götz, M., Stoykova, A., Gruss, P., 1998. Pax6 controls radial glia differentiation in the cerebral cortex. Neuron. 21, 1031–44.PubMedGoogle Scholar
  81. Gould, E., Reeves, A. J., Fallah, M., Tanapat, P., Gross, C. G., Fuchs, E., 1999a. Hippocampal neurogenesis in adult old world primates. Proc Natl Acad Sci USA. 96, 5263–7.PubMedGoogle Scholar
  82. Gould, E., Reeves, A. J., Graziano, M. S., Gross, C. G., 1999b. Neurogenesis in the neocortex of adult primates. Science. 286, 548–52.PubMedGoogle Scholar
  83. Gould, E., Vail, N., Wagers, M., Gross, C. G., 2001. Adult-generated hippocampal and neocortical neurons in macaques have a transient existence. Proc Natl Acad Sci USA. 98, 10910–7.PubMedGoogle Scholar
  84. Gross, C. G., 2000. Neurogenesis in the adult brain: death of a dogma. Nat Rev Neurosci. 1, 67–73.PubMedGoogle Scholar
  85. Gueneau, G., Privat, A., Drouet, J., Court, L., 1982. Subgranular zone of the dentate gyrus of young rabbits as a secondary matrix. A high-resolution autoradiographic study. Dev Neurosci. 5, 345–58.PubMedGoogle Scholar
  86. Guillemot, F., 2007. Cell fate specification in the mammalian telencephalon. Prog Neurobiol. 83, 37–52.PubMedGoogle Scholar
  87. Gustafsson, M. V., Zheng, X., Pereira, T., Gradin, K., Jin, S., Lundkvist, J., Ruas, J. L., Poellinger, L., Lendahl, U., Bondesson, M., 2005. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell. 9, 617–28.PubMedGoogle Scholar
  88. Han, Y. G., Spassky, N., Romaguera-Ros, M., Garcia-Verdugo, J. M., Aguilar, A., Schneider-Maunoury, S., Alvarez-Buylla, A., 2008. Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci. 11, 277–84.PubMedGoogle Scholar
  89. Hatakeyama, J., Bessho, Y., Katoh, K., Ookawara, S., Fujioka, M., Guillemot, F., Kageyama, R., 2004. Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation. Development. 131, 5539–50.PubMedGoogle Scholar
  90. Haubensak, W., Attardo, A., Denk, W., Huttner, W. B., 2004. Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci USA. 101, 3196–201.PubMedGoogle Scholar
  91. Hayes, N. L., Nowakowski, R. S., 2000. Exploiting the dynamics of S-phase tracers in developing brain: interkinetic nuclear migration for cells entering versus leaving the S-phase. Dev Neurosci. 22, 44–55.PubMedGoogle Scholar
  92. Hayes, N. L., Nowakowski, R. S., 2002. Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice. Brain Res Dev Brain Res. 134, 77–85.PubMedGoogle Scholar
  93. He, T. C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., Morin, P. J., Vogelstein, B., Kinzler, K. W., 1998. Identification of c-MYC as a target of the APC pathway. Science. 281, 1509–12.PubMedGoogle Scholar
  94. Hevner, R. F., 2006. From radial glia to pyramidal-projection neuron: transcription factor cascades in cerebral cortex development. Mol Neurobiol. 33, 33–50.PubMedGoogle Scholar
  95. Honjo, T., 1996. The shortest path from the surface to the nucleus: RBP-J kappa/Su(H) transcription factor. Genes Cells. 1, 1–9.PubMedGoogle Scholar
  96. Houbaviy, H. B., Murray, M. F., Sharp, P. A., 2003. Embryonic stem cell-specific MicroRNAs. Dev Cell. 5, 351–8.PubMedGoogle Scholar
  97. Hu, G., Lee, H., Price, S. M., Shen, M. M., Abate-Shen, C., 2001. Msx homeobox genes inhibit differentiation through upregulation of cyclin D1. Development. 128, 2373–84.PubMedGoogle Scholar
  98. Huttner, W. B., Brand, M., 1997. Asymmetric division and polarity of neuroepithelial cells. Curr Opin Neurobiol. 7, 29–39.PubMedGoogle Scholar
  99. Ichikawa, M., Shiga, T., Hirata, Y., 1983. Spatial and temporal pattern of postnatal proliferation of glial cells in the parietal cortex of the rat. Brain Res. 285, 181–7.PubMedGoogle Scholar
  100. Imayoshi, I., Sakamoto, M., Ohtsuka, T., Kageyama, R., 2009. Continuous neurogenesis in the adult brain. Dev Growth Differ. 51, 379–86.PubMedGoogle Scholar
  101. Imayoshi, I., Sakamoto, M., Ohtsuka, T., Takao, K., Miyakawa, T., Yamaguchi, M., Mori, K., Ikeda, T., Itohara, S., Kageyama, R., 2008. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci. 11, 1153–61.PubMedGoogle Scholar
  102. Ingham, P. W., McMahon, A. P., 2001. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15, 3059–87.PubMedGoogle Scholar
  103. Ishibashi, M., McMahon, A. P., 2002. A sonic hedgehog-dependent signaling relay regulates growth of diencephalic and mesencephalic primordia in the early mouse embryo. Development. 129, 4807–19.PubMedGoogle Scholar
  104. Jacob, J., Briscoe, J., 2003. Gli proteins and the control of spinal-cord patterning. EMBO Rep. 4, 761–5.PubMedGoogle Scholar
  105. Jessell, T. M., 2000. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet. 1, 20–9.PubMedGoogle Scholar
  106. Jin, K., Zhu, Y., Sun, Y., Mao, X. O., Xie, L., Greenberg, D. A., 2002. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA. 99, 11946–50.PubMedGoogle Scholar
  107. Johansson, C. B., Momma, S., Clarke, D. L., Risling, M., Lendahl, U., Frisen, J., 1999. Identification of a neural stem cell in the adult mammalian central nervous system. Cell. 96, 25–34.PubMedGoogle Scholar
  108. Kageyama, R., Nakanishi, S., 1997. Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system. Curr Opin Genet Dev. 7, 659–65.PubMedGoogle Scholar
  109. Kageyama, R., Ohtsuka, T., Kobayashi, T., 2008. Roles of Hes genes in neural development. Dev Growth Differ. 50 Suppl 1, S97–103.PubMedGoogle Scholar
  110. Kaplan, M. S., Hinds, J. W., 1977. Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science. 197, 1092–4.PubMedGoogle Scholar
  111. Kempermann, G., 2008. The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? Trends Neurosci. 31, 163–9.PubMedGoogle Scholar
  112. Kempermann, G., Gage, F. H., 2002. Genetic influence on phenotypic differentiation in adult ­hippocampal neurogenesis. Brain Res Dev Brain Res. 134, 1–12.PubMedGoogle Scholar
  113. Kempermann, G., Jessberger, S., Steiner, B., Kronenberg, G., 2004. Milestones of neuronal ­development in the adult hippocampus. Trends Neurosci. 27, 447–52.PubMedGoogle Scholar
  114. Kempermann, G., Kuhn, H. G., Gage, F. H., 1997. More hippocampal neurons in adult mice living in an enriched environment. Nature. 386, 493–5.PubMedGoogle Scholar
  115. Kenney, A. M., Cole, M. D., Rowitch, D. H., 2003. Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development. 130, 15–28.PubMedGoogle Scholar
  116. Kenney, A. M., Rowitch, D. H., 2000. Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol Cell Biol. 20, 9055-67.PubMedGoogle Scholar
  117. Kim, V. N., 2005. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 6, 376–85.PubMedGoogle Scholar
  118. Klein, M. E., Impey, S., Goodman, R. H., 2005. Role reversal: the regulation of neuronal gene expression by microRNAs. Curr Opin Neurobiol. 15, 507–13.PubMedGoogle Scholar
  119. Koketsu, D., Mikami, A., Miyamoto, Y., Hisatsune, T., 2003. Nonrenewal of neurons in the cerebral neocortex of adult macaque monkeys. J Neurosci. 23, 937–42.PubMedGoogle Scholar
  120. Komada, M., Saitsu, H., Kinboshi, M., Miura, T., Shiota, K., Ishibashi, M., 2008. Hedgehog signaling is involved in development of the neocortex. Development. 135, 2717–27.PubMedGoogle Scholar
  121. Kondziolka, D., Wechsler, L., Goldstein, S., Meltzer, C., Thulborn, K. R., Gebel, J., Jannetta, P., DeCesare, S., Elder, E. M., McGrogan, M., Reitman, M. A., Bynum, L., 2000. Transplantation of cultured human neuronal cells for patients with stroke. Neurology. 55, 565–9.PubMedGoogle Scholar
  122. Konno, D., Shioi, G., Shitamukai, A., Mori, A., Kiyonari, H., Miyata, T., Matsuzaki, F., 2008. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat Cell Biol. 10, 93–101.PubMedGoogle Scholar
  123. Korada, S., Zheng, W., Basilico, C., Schwartz, M. L., Vaccarino, F. M., 2002. Fibroblast growth factor 2 is necessary for the growth of glutamate projection neurons in the anterior neocortex. J Neurosci. 22, 863–75.PubMedGoogle Scholar
  124. Kornack, D. R., Rakic, P., 1999. Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci U S A. 96, 5768–73.PubMedGoogle Scholar
  125. Kornack, D. R., Rakic, P., 2001. Cell proliferation without neurogenesis in adult primate neocortex. Science. 294, 2127–30.PubMedGoogle Scholar
  126. Kosodo, Y., Röper, K., Haubensak, W., Marzesco, A. M., Corbeil, D., Huttner, W. B., 2004. Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells. EMBO J. 23, 2314–24.PubMedGoogle Scholar
  127. Kriegstein, A., Alvarez-Buylla, A., 2009. The Glial Nature of Embryonic and Adult Neural Stem Cells. Annu Rev Neurosci. 32, 149–184.PubMedGoogle Scholar
  128. Kriegstein, A. R., Götz, M., 2003. Radial glia diversity: a matter of cell fate. Glia. 43, 37–43.PubMedGoogle Scholar
  129. Kuhn, H. G., Dickinson-Anson, H., Gage, F. H., 1996. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci. 16, 2027–33.PubMedGoogle Scholar
  130. Kuwabara, T., Hsieh, J., Muotri, A., Yeo, G., Warashina, M., Lie, D. C., Moore, L., Nakashima, K., Asashima, M., Gage, F. H., 2009. Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nat Neurosci.12(9):1097–105PubMedGoogle Scholar
  131. Lai, K., Kaspar, B. K., Gage, F. H., Schaffer, D. V., 2003. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci. 6, 21–7.PubMedGoogle Scholar
  132. Lange, C., Huttner, W. B., Calegari, F., 2009. Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors. Cell Stem Cell. 5, 320–31.PubMedGoogle Scholar
  133. Lange, C., Mix, E., Rateitschak, K., Rolfs, A., 2006. Wnt signal pathways and neural stem cell differentiation. Neuro-degenerative diseases. 3, 76–86.Google Scholar
  134. Lathia, J. D., Mattson, M. P., Cheng, A., 2008. Notch: from neural development to neurological disorders. J Neurochem. 107, 1471–81.PubMedGoogle Scholar
  135. Lessard, J., Wu, J. I., Ranish, J. A., Wan, M., Winslow, M. M., Staahl, B. T., Wu, H., Aebersold, R., Graef, I. A., Crabtree, G. R., 2007. An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron. 55, 201–15.PubMedGoogle Scholar
  136. Leuner, B., Mendolia-Loffredo, S., Kozorovitskiy, Y., Samburg, D., Gould, E., Shors, T. J., 2004. Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J Neurosci. 24, 7477–81.PubMedGoogle Scholar
  137. Li, E., Bestor, T. H., Jaenisch, R., 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 69, 915–26.PubMedGoogle Scholar
  138. Lie, D. C., Colamarino, S. A., Song, H. J., Desire, L., Mira, H., Consiglio, A., Lein, E. S., Jessberger, S., Lansford, H., Dearie, A. R., Gage, F. H., 2005. Wnt signalling regulates adult hippocampal neurogenesis. Nature. 437, 1370–5.PubMedGoogle Scholar
  139. Liem, K. F., Tremml, G., 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, 127–38.PubMedGoogle Scholar
  140. Liu, Y., Helms, A. W., Johnson, J. E., 2004. Distinct activities of Msx1 and Msx3 in dorsal neural tube development. Development. 131, 1017–28.PubMedGoogle Scholar
  141. Lledo, P. M., Alonso, M., Grubb, M. S., 2006. Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci. 7, 179–93.PubMedGoogle Scholar
  142. Logan, C. Y., Nusse, R., 2004. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 20, 781–810.PubMedGoogle Scholar
  143. Lois, C., 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, 2074–7.PubMedGoogle Scholar
  144. Lok, J., Gupta, P., Guo, S., Kim, W. J., Whalen, M. J., van Leyen, K., Lo, E. H., 2007. Cell-cell signaling in the neurovascular unit. Neurochem Res. 32, 2032–45.PubMedGoogle Scholar
  145. Lopez-Munoz, F., Boya, J., Alamo, C., 2006. Neuron theory, the cornerstone of neuroscience, on the centenary of the nobel prize award to Santiago Ramon y Cajal. Brain Res Bull. 70, 391–405.PubMedGoogle Scholar
  146. Louissaint, A., Jr., Rao, S., Leventhal, C., Goldman, S. A., 2002. Coordinated interaction of ­neurogenesis and angiogenesis in the adult songbird brain. Neuron. 34, 945–-60.PubMedGoogle Scholar
  147. Lugert, S., Basak, O., Knuckles, P., Haussler, U., Fabel, K., Götz, M., Haas, C. A., Kempermann, G., Taylor, V., Giachino, C., 2010. Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell. 6, 445–56.PubMedGoogle Scholar
  148. Lukaszewicz, A., Savatier, P., Cortay, V., Kennedy, H., Dehay, C., 2002. Contrasting effects of basic fibroblast growth factor and neurotrophin 3 on cell cycle kinetics of mouse cortical stem cells. J Neurosci. 22, 6610–22.PubMedGoogle Scholar
  149. Machold, R., Hayashi, S., Rutlin, M., Muzumdar, M. D., Nery, S., Corbin, J. G., Gritli-Linde, A., Dellovade, T., Porter, J. A., Rubin, L. L., Dudek, H., McMahon, A. P., Fishell, G., 2003. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron. 39, 937–50.PubMedGoogle Scholar
  150. Machon, O., van den Bout, C. J., Backman, M., Kemler, R., Krauss, S., 2003. Role of beta-catenin in the developing cortical and hippocampal neuroepithelium. Neuroscience. 122, 129–43.PubMedGoogle Scholar
  151. Martí, E., Takada, R., Bumcrot, D. A., Sasaki, H., McMahon, A. P., 1995. Distribution of Sonic hedgehog peptides in the developing chick and mouse embryo. Development. 121, 2537–47.PubMedGoogle Scholar
  152. Martinez-Marcos, A., Ubeda-Banon, I., Deng, L., Halpern, M., 2000. Neurogenesis in the vomeronasal epithelium of adult rats: evidence for different mechanisms for growth and neuronal turnover. J Neurobiol. 44, 423–35.PubMedGoogle Scholar
  153. Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., Sun, Y. E., 2003. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. 302, 890–3.PubMedGoogle Scholar
  154. Mason, I., 2007. Initiation to end point: the multiple roles of fibroblast growth factors in neural development. Nat Rev Neurosci. 8, 583–96.PubMedGoogle Scholar
  155. McMahon, J. A., Takada, S., Zimmerman, L. B., Fan, C. M., Harland, R. M., McMahon, A. P., 1998. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev. 12, 1438–52.PubMedGoogle Scholar
  156. Megason, S. G., McMahon, A. P., 2002. A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development. 129, 2087–98.PubMedGoogle Scholar
  157. Meshi, D., Drew, M. R., Saxe, M., Ansorge, M. S., David, D., Santarelli, L., Malapani, C., Moore, H., Hen, R., 2006. Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nat Neurosci. 9, 729–31.PubMedGoogle Scholar
  158. Mirzadeh, Z., Merkle, F. T., Soriano-Navarro, M., Garcia-Verdugo, J. M., Alvarez-Buylla, A., 2008. Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell. 3, 265–78.PubMedGoogle Scholar
  159. Mission, J. P., Takahashi, T., Caviness, V. S., Jr., 1991. Ontogeny of radial and other astroglial cells in murine cerebral cortex. Glia. 4, 138–48.PubMedGoogle Scholar
  160. Miyata, T., Kawaguchi, A., Saito, K., Kawano, M., Muto, T., Ogawa, M., 2004. Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development. 131, 3133–45.PubMedGoogle Scholar
  161. Morin, X., Jaouen, F., Durbec, P., 2007. Control of planar divisions by the G-protein regulator LGN maintains progenitors in the chick neuroepithelium. Nat Neurosci. 10, 1440–8.PubMedGoogle Scholar
  162. Morshead, C. M., Reynolds, B. A., Craig, C. G., McBurney, M. W., Staines, W. A., Morassutti, D., Weiss, S., van der Kooy, D., 1994. Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron. 13, 1071–82.PubMedGoogle Scholar
  163. Morshead, C. M., van der Kooy, D., 1992. Postmitotic death is the fate of constitutively proliferating cells in the subependymal layer of the adult mouse brain. J Neurosci. 12, 249–56.PubMedGoogle Scholar
  164. Nakayama, K. I., Nakayama, K., 2006. Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer. 6, 369–81.PubMedGoogle Scholar
  165. Ninkovic, J., Götz, M., 2007. Signaling in adult neurogenesis: from stem cell niche to neuronal networks. Curr Opin Neurobiol. 17, 338–44.PubMedGoogle Scholar
  166. Noctor, S. C., Martínez-Cerdeño, V., Ivic, L., Kriegstein, A. R., 2004. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci. 7, 136–44.PubMedGoogle Scholar
  167. Noctor, S. C., Martínez-Cerdeño, V., Kriegstein, A. R., 2008. Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J Comp Neurol. 508, 28–44.PubMedGoogle Scholar
  168. Nottebohm, F., 1985. Neuronal replacement in adulthood. Ann N Y Acad Sci. 457, 143–61.PubMedGoogle Scholar
  169. Nusse, R., Fuerer, C., Ching, W., Harnish, K., Logan, C., Zeng, A., ten Berge, D., Kalani, Y., 2008. Wnt signaling and stem cell control. Cold Spring Harb Symp Quant Biol. 73, 59–66.PubMedGoogle Scholar
  170. Nyfeler, Y., Kirch, R. D., Mantei, N., Leone, D. P., Radtke, F., Suter, U., Taylor, V., 2005. Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal. EMBO J. 24, 3504–15.PubMedGoogle Scholar
  171. Ochiai, W., Nakatani, S., Takahara, T., Kainuma, M., Masaoka, M., Minobe, S., Namihira, M., Nakashima, K., Sakakibara, A., Ogawa, M., Miyata, T., 2009. Periventricular notch activation and asymmetric Ngn2 and Tbr2 expression in pair-generated neocortical daughter cells. Mol Cell Neurosci. 40, 225–33.PubMedGoogle Scholar
  172. Ohnuma, S., Harris, W. A., 2003. Neurogenesis and the cell cycle. Neuron. 40, 199–208.PubMedGoogle Scholar
  173. Ohnuma, S., Philpott, A., Harris, W. A., 2001. Cell cycle and cell fate in the nervous system. Curr Opin Neurobiol. 11, 66–73.PubMedGoogle Scholar
  174. Ohtsuka, T., Ishibashi, M., Gradwohl, G., Nakanishi, S., Guillemot, F., Kageyama, R., 1999. Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation. EMBO J. 18, 2196–207.PubMedGoogle Scholar
  175. Okano, H., 2002. Stem cell biology of the central nervous system. J Neurosci Res. 69, 698–707.PubMedGoogle Scholar
  176. Okano, H., Sakaguchi, M., Ohki, K., Suzuki, N., Sawamoto, K., 2007. Regeneration of the central nervous system using endogenous repair mechanisms. J Neurochem. 102, 1459–65.PubMedGoogle Scholar
  177. Okano, H., Sawamoto, K., 2008. Neural stem cells: involvement in adult neurogenesis and CNS repair. Philos Trans R Soc Lond, B, Biol Sci. 363, 2111–22.PubMedGoogle Scholar
  178. Okano, M., Bell, D. W., Haber, D. A., Li, E., 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 99, 247–57.PubMedGoogle Scholar
  179. Olson, A. K., Eadie, B. D., Ernst, C., Christie, B. R., 2006. Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus. 16, 250–60.PubMedGoogle Scholar
  180. Osumi, N., Shinohara, H., Numayama-Tsuruta, K., Maekawa, M., 2008. Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. Stem Cells. 26, 1663–72.PubMedGoogle Scholar
  181. Palmer, T. D., Willhoite, A. R., Gage, F. H., 2000. Vascular niche for adult hippocampal neurogenesis. J Comp Neurol. 425, 479–94.PubMedGoogle Scholar
  182. Panchision, D. M., 2009. The role of oxygen in regulating neural stem cells in development and disease. J Cell Physiol. 220, 562–8.PubMedGoogle Scholar
  183. Panchision, D. M., Pickel, J. M., Studer, L., Lee, S. H., Turner, P. A., Hazel, T. G., McKay, R. D., 2001. Sequential actions of BMP receptors control neural precursor cell production and fate. Genes Dev. 15, 2094–110.PubMedGoogle Scholar
  184. Parr, B. A., Shea, M. J., Vassileva, G., McMahon, A. P., 1993. Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development. 119, 247–61.PubMedGoogle Scholar
  185. Parras, C. M., Schuurmans, C., Scardigli, R., Kim, J., Anderson, D. J., Guillemot, F., 2002. Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity. Genes Dev. 16, 324–38.PubMedGoogle Scholar
  186. Perez, S. E., Rebelo, S., Anderson, D. J., 1999. Early specification of sensory neuron fate revealed by expression and function of neurogenins in the chick embryo. Development. 126, 1715–28.PubMedGoogle Scholar
  187. Pierani, A., Brenner-Morton, S., Chiang, C., Jessell, T. M., 1999. A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Cell. 97, 903–15.PubMedGoogle Scholar
  188. Pierani, A., Moran-Rivard, L., Sunshine, M. J., Littman, D. R., Goulding, M., Jessell, T. M., 2001. Control of interneuron fate in the developing spinal cord by the progenitor homeodomain protein Dbx1. Neuron. 29, 367–84.PubMedGoogle Scholar
  189. Pilaz, L. J., Patti, D., Marcy, G., Ollier, E., Pfister, S., Douglas, R. J., Betizeau, M., Gautier, E., Cortay, V., Doerflinger, N., Kennedy, H., Dehay, C., 2009. Forced G1-phase reduction alters mode of division, neuron number, and laminar phenotype in the cerebral cortex. Proc Natl Acad Sci USA. 62 (4): 455–7.Google Scholar
  190. Pistollato, F., Chen, H. L., Schwartz, P. H., Basso, G., Panchision, D. M., 2007. Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes. Mol Cell Neurosci. 35, 424–35.PubMedGoogle Scholar
  191. Pollard, S. M., Wallbank, R., Tomlinson, S., Grotewold, L., Smith, A., 2008. Fibroblast growth factor induces a neural stem cell phenotype in foetal forebrain progenitors and during embryonic stem cell differentiation. Mol Cell Neurosci. 38, 393–403.PubMedGoogle Scholar
  192. Qian, X., Shen, Q., Goderie, S. K., He, W., Capela, A., Davis, A. A., Temple, S., 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.PubMedGoogle Scholar
  193. Raballo, R., Rhee, J., Lyn-Cook, R., Leckman, J. F., Schwartz, M. L., Vaccarino, F. M., 2000. Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J Neurosci. 20, 5012–23.PubMedGoogle Scholar
  194. Ramon y Cajal,s 1913. Degeneracion y regeneracion de los niervos. Imprenta de hijos de Nicolas Moya, Madrid.Google Scholar
  195. Reynolds, B. A., Tetzlaff, W., Weiss, S., 1992. A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci. 12, 4565–74.PubMedGoogle Scholar
  196. Reynolds, B. A., Weiss, S., 1992. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 255, 1707–10.PubMedGoogle Scholar
  197. Reynolds, B. A., 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
  198. Ringe, J., Kaps, C., Burmester, G. R., Sittinger, M., 2002. Stem cells for regenerative medicine: advances in the engineering of tissues and organs. Naturwissenschaften. 89, 338–51.PubMedGoogle Scholar
  199. Robertson, K. D., Wolffe, A. P., 2000. DNA methylation in health and disease. Nat Rev Genet. 1, 11–9.PubMedGoogle Scholar
  200. Ross, S. E., Greenberg, M. E., Stiles, C. D., 2003. Basic helix-loop-helix factors in cortical development. Neuron. 39, 13–25.PubMedGoogle Scholar
  201. Rottach, A., Leonhardt, H., Spada, F., 2009. DNA methylation-mediated epigenetic control. J Cell Biochem. 108, 43–51.PubMedGoogle Scholar
  202. Sanai, N., Berger, M. S., Garcia-Verdugo, J. M., Alvarez-Buylla, A., 2007. Comment on “Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension”. Science. 318, 393; author reply 393.Google Scholar
  203. Salomoni, P., Calegari, F., 2010. Cell cycle control of mammalian neural strem cells: putting a speed limit on Gi. Trends cell Biol. 20, 233–42.Google Scholar
  204. Sansom, S. N., Griffiths, D. S., Faedo, A., Kleinjan, D. J., Ruan, Y., Smith, J., van Heyningen, V., Rubenstein, J. L., Livesey, F. J., 2009. The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis. PLoS Genet. 5, e1000511.PubMedGoogle Scholar
  205. Saxe, M. D., Battaglia, F., Wang, J. W., Malleret, G., David, D. J., Monckton, J. E., Garcia, A. D., Sofroniew, M. V., Kandel, E. R., Santarelli, L., Hen, R., Drew, M. R., 2006. Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci U S A. 103, 17501–6.PubMedGoogle Scholar
  206. Seri, B., Garcia-Verdugo, J. M., McEwen, B. S., Alvarez-Buylla, A., 2001. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci. 21, 7153–60.PubMedGoogle Scholar
  207. Seroogy, K. B., Gall, C. M., Lee, D. C., Kornblum, H. I., 1995. Proliferative zones of postnatal rat brain express epidermal growth factor receptor mRNA. Brain Res. 670, 157–64.PubMedGoogle Scholar
  208. Shastri, V. P., 2006. Future of regenerative medicine: challenges and hurdles. Artif Organs. 30, 828–34.PubMedGoogle Scholar
  209. Shen, Q., Wang, Y., Kokovay, E., Lin, G., Chuang, S. M., Goderie, S. K., Roysam, B., Temple, S., 2008. Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell. 3, 289–300.PubMedGoogle Scholar
  210. Shi, Y., Massagué, J., 2003. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 113, 685–700.PubMedGoogle Scholar
  211. Shi, Y., Sun, G., Zhao, C., Stewart, R., 2008. Neural stem cell self-renewal. Crit Rev Oncol Hematol. 65, 43–53.PubMedGoogle Scholar
  212. Shimogori, T., Banuchi, V., Ng, H. Y., Strauss, J. B., Grove, E. A., 2004. Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex. Development. 131, 5639–47.PubMedGoogle Scholar
  213. Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., Ben-Ze’ev, A., 1999. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA. 96, 5522–7.PubMedGoogle Scholar
  214. Simpson, T. I., Price, D. J., 2002. Pax6; a pleiotropic player in development. Bioessays. 24, 1041–51.PubMedGoogle Scholar
  215. Smirnova, L., Gräfe, A., Seiler, A., Schumacher, S., Nitsch, R., Wulczyn, F. G., 2005. Regulation of miRNA expression during neural cell specification. Eur J Neurosci. 21, 1469–77.PubMedGoogle Scholar
  216. Stanfield, B. B., Trice, J. E., 1988. Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections. Exp Brain Res. 72, 399–406.PubMedGoogle Scholar
  217. Steiner, B., Wolf, S., Kempermann, G., 2006. Adult neurogenesis and neurodegenerative disease. Regen Med. 1, 15–28.PubMedGoogle Scholar
  218. Storm, E. E., Garel, S., Borello, U., Hebert, J. M., Martinez, S., McConnell, S. K., Martin, G. R., Rubenstein, J. L., 2006. Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers. Development. 133, 1831–44.PubMedGoogle Scholar
  219. Stoykova, A., Fritsch, R., Walther, C., Gruss, P., 1996. Forebrain patterning defects in Small eye mutant mice. Development. 122, 3453–65.PubMedGoogle Scholar
  220. Strahl, B. D., Allis, C. D., 2000. The language of covalent histone modifications. Nature. 403, 41–5.PubMedGoogle Scholar
  221. Suh, H., Deng, W., Gage, F. H., 2009. Signaling in Adult Neurogenesis. Annu Rev Cell Dev Biol. 5, 377–406.Google Scholar
  222. Suh, M. R., Lee, Y., Kim, J. Y., Kim, S. K., Moon, S. H., Lee, J. Y., Cha, K. Y., Chung, H. M., Yoon, H. S., Moon, S. Y., Kim, V. N., Kim, K. S., 2004. Human embryonic stem cells express a unique set of microRNAs. Dev Biol. 270, 488–98.PubMedGoogle Scholar
  223. Sun, G., Yu, R. T., Evans, R. M., Shi, Y., 2007. Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc Natl Acad Sci USA. 104, 15282–7.PubMedGoogle Scholar
  224. Takahashi, K., Yamanaka, S., 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126, 663–76.PubMedGoogle Scholar
  225. Takahashi, T., Nowakowski, R. S., Caviness, V. S., 1995. The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J Neurosci. 15, 6046–57.PubMedGoogle Scholar
  226. Takizawa, T., Nakashima, K., Namihira, M., Ochiai, W., Uemura, A., Yanagisawa, M., Fujita, N., Nakao, M., Taga, T., 2001. DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain. Dev Cell. 1, 749–58.PubMedGoogle Scholar
  227. Tavazoie, M., Van der Veken, L., Silva-Vargas, V., Louissaint, M., Colonna, L., Zaidi, B., ­Garcia-Verdugo, J. M., Doetsch, F., 2008. A specialized vascular niche for adult neural stem cells. Cell Stem Cell. 3, 279–88.PubMedGoogle Scholar
  228. Tetsu, O., McCormick, F., 1999. Beta-catenin regulates expression of cyclin D1 in colon ­carcinoma cells. Nature. 398, 422–6.PubMedGoogle Scholar
  229. Toresson, H., Potter, S. S., Campbell, K., 2000. Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2. Development. 127, 4361–71.PubMedGoogle Scholar
  230. Toni, N., Laplagne, D. A., Zhao, C., Lombardi, G., Ribak, C. E., Gage, F. H., Schinder, A. F., 2008. Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci. 11, 901–7.PubMedGoogle Scholar
  231. Turner, B. M., 2002. Cellular memory and the histone code. Cell. 111, 285–91.PubMedGoogle Scholar
  232. Ulloa, F., Briscoe, J., 2007. Morphogens and the control of cell proliferation and patterning in the spinal cord. Cell Cycle. 6, 2640–9.PubMedGoogle Scholar
  233. Vaccarino, F. M., Schwartz, M. L., Raballo, R., Nilsen, J., Rhee, J., Zhou, M., Doetschman, T., Coffin, J. D., Wyland, J. J., Hung, Y. T., 1999a. Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat Neurosci. 2, 246–53.PubMedGoogle Scholar
  234. Vaccarino, F. M., Schwartz, M. L., Raballo, R., Rhee, J., Lyn-Cook, R., 1999b. Fibroblast growth factor signaling regulates growth and morphogenesis at multiple steps during brain development. Curr Top Dev Biol. 46, 179–200.PubMedGoogle Scholar
  235. van Praag, H., Schinder, A. F., Christie, B. R., Toni, N., Palmer, T. D., Gage, F. H., 2002. Functional neurogenesis in the adult hippocampus. Nature. 415, 1030–4.PubMedGoogle Scholar
  236. Vincent, A., Van Seuningen, I., 2009. Epigenetics, stem cells and epithelial cell fate. Differentiation.78,99–107.PubMedGoogle Scholar
  237. Visvanathan, J., Lee, S., Lee, B., Lee, J. W., Lee, S. K., 2007. The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev. 21, 744–9.PubMedGoogle Scholar
  238. Viti, J., Gulacsi, A., Lillien, L., 2003. Wnt regulation of progenitor maturation in the cortex depends on Shh or fibroblast growth factor 2. J Neurosci. 23, 5919–27.PubMedGoogle Scholar
  239. Voigt, T., 1989. 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.PubMedGoogle Scholar
  240. Wang, Y., Yang, J., Zheng, H., Tomasek, G. J., Zhang, P., McKeever, P. E., Lee, E. Y., Zhu, Y., 2009. Expression of mutant p53 proteins implicates a lineage relationship between neural stem cells and malignant astrocytic glioma in a murine model. Cancer Cell. 15, 514–26.PubMedGoogle Scholar
  241. Warren, N., Caric, D., Pratt, T., Clausen, J. A., Asavaritikrai, P., Mason, J. O., Hill, R. E., Price, D. J., 1999. The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex. Cereb Cortex. 9, 627–35.PubMedGoogle Scholar
  242. Watanabe, D., Suetake, I., Tada, T., Tajima, S., 2002. Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech Dev. 118, 187–90.PubMedGoogle Scholar
  243. Watanabe, D., Uchiyama, K., Hanaoka, K., 2006. Transition of mouse de novo methyltransferases expression from Dnmt3b to Dnmt3a during neural progenitor cell development. Neuroscience. 142, 727–37.PubMedGoogle Scholar
  244. Wenning, G. K., Odin, P., Morrish, P., Rehncrona, S., Widner, H., Brundin, P., Rothwell, J. C., Brown, R., Gustavii, B., Hagell, P., Jahanshahi, M., Sawle, G., Bjorklund, A., Brooks, D. J., Marsden, C. D., Quinn, N. P., Lindvall, O., 1997. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson’s disease. Ann Neurol. 42, 95–107.PubMedGoogle Scholar
  245. Wine-Lee, L., Ahn, K. J., Richardson, R. D., Mishina, Y., Lyons, K. M., Crenshaw, E. B., 2004. Signaling through BMP type 1 receptors is required for development of interneuron cell types in the dorsal spinal cord. Development. 131, 5393–403.PubMedGoogle Scholar
  246. Wolpert, L., 1969. Positional information and the spatial pattern of cellular differentiation. J Theor Biol. 25, 1–47.PubMedGoogle Scholar
  247. Yoon, K., Nery, S., Rutlin, M. L., Radtke, F., Fishell, G., Gaiano, N., 2004. Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors. J Neurosci. 24, 9497–506.PubMedGoogle Scholar
  248. Zechner, D., Fujita, Y., Hülsken, J., Müller, T., Walther, I., Taketo, M. M., Crenshaw, E. B., Birchmeier, W., Birchmeier, C., 2003. beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev Biol. 258, 406–18.PubMedGoogle Scholar
  249. Zhang, C. L., Zou, Y., He, W., Gage, F. H., Evans, R. M., 2008a. A role for adult TLX-positive neural stem cells in learning and behaviour. Nature. 451, 1004–7.PubMedGoogle Scholar
  250. Zhang, R. L., Zhang, Z. G., Chopp, M., 2008b. Ischemic stroke and neurogenesis in the subventricular zone. Neuropharmacology. 55, 345–52.PubMedGoogle Scholar
  251. Zhang, R. L., Zhang, Z. G., Lu, M., Wang, Y., Yang, J. J., Chopp, M., 2006. Reduction of the cell cycle length by decreasing G1 phase and cell cycle reentry expand neuronal progenitor cells in the subventricular zone of adult rat after stroke. J Cereb Blood Flow Metab. 26, 857–63.PubMedGoogle Scholar
  252. Zhang, Z. G., Chopp, M., 2009. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet neurology. 8, 491–500.PubMedGoogle Scholar
  253. Zhao, C., Deng, W., Gage, F. H., 2008. Mechanisms and functional implications of adult neurogenesis. Cell. 132, 645–60.PubMedGoogle Scholar
  254. Zhu, J., Zhou, L., XingWu, F., 2006. Tracking neural stem cells in patients with brain trauma. N Engl J Med. 355, 2376–8.PubMedGoogle Scholar
  255. Zuccato, C., Cattaneo, E., 2009. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol. 5, 311–22.PubMedGoogle Scholar

Copyright information

© Springer Netherlands 2011

Authors and Affiliations

  • Yoko Arai
    • 1
  • Wieland B. Huttner
    • 1
  • Federico Calegari
    • 2
  1. 1.Max-Planck-Institute of Molecular Cell Biology and GeneticsDresdenGermany
  2. 2.Center for Regenerative TherapiesTechnische Universität Dresden, c/o: Max-Planck-Institute of Molecular Cell Biology and GeneticsDresdenGermany

Personalised recommendations