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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AP:
-
anterior-posterior
- AraC:
-
arabinosyde-C
- bHLH:
-
basic helix-loop-helix
- BMP:
-
bone morphogenic protein
- BrdU:
-
bromodeoxyuridine
- CSL:
-
CBF1/RBPJk/Supplessor of hairless/Lag1
- CNS:
-
central nervous system
- CDK:
-
cyclin-dependent kinase
- Dnmts:
-
DNA methyltransferases
- DV:
-
dorso-ventral
- EGF:
-
epidermal growth factor
- FGF2:
-
fibroblast growth factor 2
- GABA:
-
γ-aminobutyric acid
- HATs:
-
histone acetylases
- HDACs:
-
histone deacetylases
- HIF-Ia:
-
hypoxia-inducible factor Iα
- INM:
-
interkinetic nuclear migration
- miRNAs:
-
microRNAs
- NSC:
-
Neural stem cells
- Ngn:
-
neurogenin
- NICD:
-
notch receptor
- RA:
-
retinoic acid
- Shh:
-
sonic hedgehog
- SGZ:
-
subgranular zone
- SVZ:
-
sub-ventricular zone
- VZ:
-
ventricular zone
References
Abrous DN, Koehl M, Le Moal M (2005) Adult neurogenesis: from precursors to network and physiology. Physiol Rev 85:523–569
Ackman JB, Siddiqi F, Walikonis RS, LoTurco JJ (2006) Fusion of microglia with pyramidal neurons after retroviral infection. J Neurosci 26:11413–11422
Ahn S, Joyner AL (2005) In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog. Nature 437:894–897
Aigner S, Denli AM, Gage FH (2007) A novel model for an older remodeler: the BAF swap in neurogenesis. Neuron 55:171–173
Alcantara Llaguno S, Chen J, Kwon CH, Jackson EL, Li Y, Burns DK, Alvarez-Buylla A, Parada LF (2009) Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15:45–56
Alonso M, Viollet C, Gabellec MM, Meas-Yedid V, Olivo-Marin JC, Lledo PM (2006) Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb. J Neurosci 26:10508–10513
Altman J (1962) Are new neurons formed in the brains of adult mammals? Science 135:1127–1128
Alvarez-Buylla A, Lim DA (2004) For the long run: maintaining germinal niches in the adult brain. Neuron 41:683–686
Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355
Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, McKay RD (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442:823–826
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 25:9752–9761
Arias-Carrion O, Yuan TF (2009) Autologous neural stem cell transplantation: a new treatment option for Parkinson’s disease? Med Hypotheses 73:757–759
Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776
Attardo A, Calegari F, Haubensak W, Wilsch-Bräuninger M, Huttner WB (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
Barry D, McDermott K (2005) Differentiation of radial glia from radial precursor cells and transformation into astrocytes in the developing rat spinal cord. Glia 50:187–197
Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233
Bautch VL, James JM (2009) Neurovascular development: the beginning of a beautiful friendship. Cell Adh Migr 3:199–204
Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, Mills AA, Elledge SJ, Anderson KV, Hannon GJ (2003) Dicer is essential for mouse development. Nat Genet 35:215–217
Biron VL, McManus KJ, Hu N, Hendzel MJ, Underhill DA (2004) Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development. Dev Biol 276:337–351
Borello U, Cobos I, Long JE, McWhirter JR, Murre C, Rubenstein JL (2008) FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development. Neural Dev 3:17
BoulderComm (1970) Embryonic vertebrate central nervous system: revised terminology. The Boulder Committee. Anat Rec 166:257–261
Breunig JJ, Arellano JI, Macklis JD, Rakic P (2007a) Everything that glitters isn’t gold: a critical review of postnatal neural precursor analyses. Cell Stem Cell 1:612–627
Breunig JJ, Silbereis J, Vaccarino FM, Sestan N, Rakic P (2007b) Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus. Proc Natl Acad Sci U S A 104:20558–20563
Breunig JJ, Sarkisian MR, Arellano JI, Morozov YM, Ayoub AE, Sojitra S, Wang B, Flavell RA, Rakic P, Town T (2008) Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling. Proc Natl Acad Sci U S A 105:13127–13132
Brinton RD, Wang JM (2006) Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer’s disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res 3:185–190
Briscoe J, Pierani A, Jessell TM, Ericson J (2000) A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 101:435–445
Calegari F, Haubensak W, Haffner C, Huttner WB (2005) Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development. J Neurosci 25:6533–6538
Cameron HA, McKay RD (2001) Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 435:406–417
Cao L, Jiao X, Zuzga DS, Liu Y, Fong DM, Young D, During MJ (2004) VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 36:827–835
Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH (2006) Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 29:77–103
Cao X, Pfaff SL, Gage FH (2007) A functional study of miR-124 in the developing neural tube. Genes Dev 21:531–536
Capela A, Temple S (2002) LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron 35:865–875
Carlen M, Meletis K, Goritz C, Darsalia V, Evergren E, Tanigaki K, Amendola M, Barnabe-Heider F, Yeung MS, Naldini L, Honjo T, Kokaia Z, Shupliakov O, Cassidy RM, Lindvall O, Frisen J (2009) Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci 12:259–267
Castro DS, Skowronska-Krawczyk D, Armant O, Donaldson IJ, Parras C, Hunt C, Critchley JA, Nguyen L, Gossler A, Göttgens B, Matter JM, Guillemot F (2006) Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif. Dev Cell 11:831–844
Caviness VS, Takahashi T, Nowakowski RS (1995) Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model. Trends Neurosci 18:379–383
Cayuso J, Martí E (2005) Morphogens in motion: growth control of the neural tube. J Neurobiol 64:376–387
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 133:517–528
Cheng LC, Tavazoie M, Doetsch F (2005) Stem cells: from epigenetics to microRNAs. Neuron 46:363–367
Cheng LC, Pastrana E, Tavazoie M, Doetsch F (2009) miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci 12:399–408
Chenn A, McConnell SK (1995) Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis. Cell 82:631–641
Chenn A, Walsh CA (2003) Increased neuronal production, enlarged forebrains and cytoarchitectural distortions in beta-catenin overexpressing transgenic mice. Cereb Cortex 13:599–606
Chesnutt C, Burrus LW, Brown AM, Niswander L (2004) Coordinate regulation of neural tube patterning and proliferation by TGFbeta and WNT activity. Dev Biol 274:334–347
Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA (1996) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383:407–413
Chiasson BJ, Tropepe V, Morshead CM, 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
Chojnacki AK, Mak GK, Weiss S (2009) Identity crisis for adult periventricular neural stem cells: subventricular zone astrocytes, ependymal cells or both? Nat Rev Neurosci 10:153–163
Colleoni F, Torrente Y (2008) The new challenge of stem cell: brain tumour therapy. Cancer Lett 272:1–11
Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holtas S, van Roon-Mom WM, Bjork-Eriksson T, Nordborg C, Frisen J, Dragunow M, Faull RL, Eriksson PS (2007) Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315:1243–1249
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 128:5201–5212
Dayer AG, Cleaver KM, Abouantoun T, Cameron HA (2005) New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol 168:415–427
De Pietri Tonelli D, Pulvers JN, Haffner C, Murchison EP, Hannon GJ, Huttner WB (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 135:3911–3921
Dehay C, Kennedy H (2007) Cell-cycle control and cortical development. Nat Rev Neurosci 8:438–450
Dickinson ME, Krumlauf R, McMahon AP (1994) Evidence for a mitogenic effect of Wnt-1 in the developing mammalian central nervous system. Development 120:1453–1471
Diez del Corral R, Breitkreuz DN, Storey KG (2002) Onset of neuronal differentiation is regulated by paraxial mesoderm and requires attenuation of FGF signalling. Development 129:1681–1691
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
Doe CQ, Skeath JB (1996) Neurogenesis in the insect central nervous system. Curr Opin Neurobiol 6:18–24
Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 17:5046–5061
Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999a) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716
Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1999b) Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci U S A 96:11619–11624
Du T, Zamore PD (2005) microPrimer: the biogenesis and function of microRNA. Development 132:4645–4652
Ekholm SV, Reed SI (2000) Regulation of G(1) cyclin-dependent kinases in the mammalian cell cycle. Curr Opin Cell Biol 12:676–684
Erecińska M, Silver IA (2001) Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol 128:263–276
Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317
Estivill-Torrus G, Pearson H, van Heyningen V, Price DJ, 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 129:455–466
Ever L, Gaiano N (2005) Radial ‘glial’ progenitors: neurogenesis and signaling. Curr Opin Neurobiol 15:29–33
Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, Kuo CJ, Palmer TD (2003) VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci 18:2803–2812
Fan G, Martinowich K, Chin MH, He F, Fouse SD, Hutnick L, Hattori D, Ge W, Shen Y, Wu H, ten Hoeve J, Shuai K, Sun YE (2005) DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development 132:3345–3356
Farkas LM, Huttner WB (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 20:707–715
Filippov V, Kronenberg G, Pivneva T, Reuter K, Steiner B, Wang LP, 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 23:373–382
Firket H, Verly WG (1958) Autoradiographic visualization of synthesis of deoxyribonucleic acid in tissue culture with tritium-labelled thymidine. Nature 181:274–275
Fish JL, Kosodo Y, Enard W, Pääbo S, Huttner WB (2006) Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc Natl Acad Sci U S A 103:10438–10443
Fish JL, Dehay C, Kennedy H, Huttner WB (2008) Making bigger brains-the evolution of neural-progenitor-cell division. J Cell Sci 121:2783–2793
Fode C, Ma Q, Casarosa S, Ang SL, Anderson DJ, Guillemot F (2000) A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev 14:67–80
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 U S A 101:10177–10182
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 23:9357–9366
Gavin BJ, McMahon JA, McMahon AP (1990) Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development. Genes Dev 4:2319–2332
Gerdes JM, Davis EE, Katsanis N (2009) The vertebrate primary cilium in development, homeostasis, and disease. Cell 137:32–45
Givogri MI, de Planell M, Galbiati F, Superchi D, Gritti A, Vescovi A, de Vellis J, Bongarzone ER (2006) Notch signaling in astrocytes and neuroblasts of the adult subventricular zone in health and after cortical injury. Dev Neurosci 28:81–91
Götz M, Huttner WB (2005) The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6:777–788
Götz M, Stoykova A, Gruss P (1998) Pax6 controls radial glia differentiation in the cerebral cortex. Neuron 21:1031–1044
Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E (1999a) Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci U S A 96:5263–5267
Gould E, Reeves AJ, Graziano MS, Gross CG (1999b) Neurogenesis in the neocortex of adult primates. Science 286:548–552
Gould E, Vail N, Wagers M, Gross CG (2001) Adult-generated hippocampal and neocortical neurons in macaques have a transient existence. Proc Natl Acad Sci U S A 98:10910–10917
Gross CG (2000) Neurogenesis in the adult brain: death of a dogma. Nat Rev Neurosci 1:67–73
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 5:345–358
Guillemot F (2007) Cell fate specification in the mammalian telencephalon. Prog Neurobiol 83:37–52
Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, Ruas JL, Poellinger L, Lendahl U, Bondesson M (2005) Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 9:617–628
Han YG, Spassky N, Romaguera-Ros M, Garcia-Verdugo JM, 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 11:277–284
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 131:5539–5550
Haubensak W, Attardo A, Denk W, Huttner WB (2004) Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A 101:3196–3201
Hayes NL, Nowakowski RS (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
Hayes NL, Nowakowski RS (2002) Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice. Brain Res Dev Brain Res 134:77–85
He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512
Hevner RF (2006) From radial glia to pyramidal-projection neuron: transcription factor cascades in cerebral cortex development. Mol Neurobiol 33:33–50
Honjo T (1996) The shortest path from the surface to the nucleus: RBP-J kappa/Su(H) transcription factor. Genes Cells 1:1–9
Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific MicroRNAs. Dev Cell 5:351–358
Hu G, Lee H, Price SM, Shen MM, Abate-Shen C (2001) Msx homeobox genes inhibit differentiation through upregulation of cyclin D1. Development 128:2373–2384
Huttner WB, Brand M (1997) Asymmetric division and polarity of neuroepithelial cells. Curr Opin Neurobiol 7:29–39
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 285:181–187
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 11:1153–1161
Imayoshi I, Sakamoto M, Ohtsuka T, Kageyama R (2009) Continuous neurogenesis in the adult brain. Dev Growth Differ 51:379–386
Ingham PW, McMahon AP (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15:3059–3087
Ishibashi M, McMahon AP (2002) A sonic hedgehog-dependent signaling relay regulates growth of diencephalic and mesencephalic primordia in the early mouse embryo. Development 129:4807–4819
Jacob J, Briscoe J (2003) Gli proteins and the control of spinal-cord patterning. EMBO Rep 4:761–765
Jessell TM (2000) Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 1:20–29
Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A 99:11946–11950
Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96:25–34
Kageyama R, Nakanishi S (1997) Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system. Curr Opin Genet Dev 7:659–665
Kageyama R, Ohtsuka T, Kobayashi T (2008) Roles of Hes genes in neural development. Dev Growth Differ 50(Suppl 1):S97–S103
Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197:1092–1094
Kempermann G (2008) The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? Trends Neurosci 31:163–169
Kempermann G, Gage FH (2002) Genetic influence on phenotypic differentiation in adult hippocampal neurogenesis. Brain Res Dev Brain Res 134:1–12
Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495
Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27:447–452
Kenney AM, Rowitch DH (2000) Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol Cell Biol 20:9055–9067
Kenney AM, Cole MD, Rowitch DH (2003) Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 130:15–28
Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6:376–385
Klein ME, Impey S, Goodman RH (2005) Role reversal: the regulation of neuronal gene expression by microRNAs. Curr Opin Neurobiol 15:507–513
Koketsu D, Mikami A, Miyamoto Y, Hisatsune T (2003) Nonrenewal of neurons in the cerebral neocortex of adult macaque monkeys. J Neurosci 23:937–942
Komada M, Saitsu H, Kinboshi M, Miura T, Shiota K, Ishibashi M (2008) Hedgehog signaling is involved in development of the neocortex. Development 135:2717–2727
Kondziolka D, Wechsler L, Goldstein S, Meltzer C, Thulborn KR, Gebel J, Jannetta P, DeCesare S, Elder EM, McGrogan M, Reitman MA, Bynum L (2000) Transplantation of cultured human neuronal cells for patients with stroke. Neurology 55:565–569
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
Korada S, Zheng W, Basilico C, Schwartz ML, Vaccarino FM (2002) Fibroblast growth factor 2 is necessary for the growth of glutamate projection neurons in the anterior neocortex. J Neurosci 22:863–875
Kornack DR, Rakic P (1999) Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci U S A 96:5768–5773
Kornack DR, Rakic P (2001) Cell proliferation without neurogenesis in adult primate neocortex. Science 294:2127–2130
Kosodo Y, Röper K, Haubensak W, Marzesco AM, Corbeil D, Huttner WB (2004) Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells. EMBO J 23:2314–2324
Kriegstein A, Alvarez-Buylla A (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32:149–184
Kriegstein AR, Götz M (2003) Radial glia diversity: a matter of cell fate. Glia 43:37–43
Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033
Kuwabara T, Hsieh J, Muotri A, Yeo G, Warashina M, Lie DC, Moore L, Nakashima K, Asashima M, Gage FH (2009) Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nat Neurosci 12:1097–1105
Lai K, Kaspar BK, Gage FH, Schaffer DV (2003) Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci 6:21–27
Lange C, Mix E, Rateitschak K, Rolfs A (2006) Wnt signal pathways and neural stem cell differentiation. Neurodegener Dis 3:76–86
Lange C, Huttner WB, 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 5:320–331
Lathia JD, Mattson MP, Cheng A (2008) Notch: from neural development to neurological disorders. J Neurochem 107:1471–1481
Lessard J, Wu JI, Ranish JA, Wan M, Winslow MM, Staahl BT, Wu H, Aebersold R, Graef IA, Crabtree GR (2007) An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron 55:201–215
Leuner B, Mendolia-Loffredo S, Kozorovitskiy Y, Samburg D, Gould E, Shors TJ (2004) Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J Neurosci 24:7477–7481
Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926
Lie DC, Colamarino SA, Song HJ, Desire L, Mira H, Consiglio A, Lein ES, Jessberger S, Lansford H, Dearie AR, Gage FH (2005) Wnt signalling regulates adult hippocampal neurogenesis. Nature 437:1370–1375
Liem KF, Tremml G, Jessell TM (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
Liu Y, Helms AW, Johnson JE (2004) Distinct activities of Msx1 and Msx3 in dorsal neural tube development. Development 131:1017–1028
Lledo PM, Alonso M, Grubb MS (2006) Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7:179–193
Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810
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 U S A 90:2074–2077
Lok J, Gupta P, Guo S, Kim WJ, Whalen MJ, van Leyen K, Lo EH (2007) Cell-cell signaling in the neurovascular unit. Neurochem Res 32:2032–2045
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
Louissaint A Jr, Rao S, Leventhal C, Goldman SA (2002) Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron 34:945–960
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 22:6610–6622
Machold R, Hayashi S, Rutlin M, Muzumdar MD, Nery S, Corbin JG, Gritli-Linde A, Dellovade T, Porter JA, Rubin LL, Dudek H, McMahon AP, Fishell G (2003) Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 39:937–950
Machon O, van den Bout CJ, Backman M, Kemler R, Krauss S (2003) Role of beta-catenin in the developing cortical and hippocampal neuroepithelium. Neuroscience 122:129–143
Martí E, Takada R, Bumcrot DA, Sasaki H, McMahon AP (1995) Distribution of Sonic hedgehog peptides in the developing chick and mouse embryo. Development 121:2537–2547
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 44:423–435
Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302:890–893
Mason I (2007) Initiation to end point: the multiple roles of fibroblast growth factors in neural development. Nat Rev Neurosci 8:583–596
McMahon JA, Takada S, Zimmerman LB, Fan CM, Harland RM, McMahon AP (1998) Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12:1438–1452
Megason SG, McMahon AP (2002) A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development 129:2087–2098
Meshi D, Drew MR, Saxe M, Ansorge MS, David D, Santarelli L, Malapani C, Moore H, Hen R (2006) Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nat Neurosci 9:729–731
Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, 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 3:265–278
Mission JP, Takahashi T, Caviness VS Jr (1991) Ontogeny of radial and other astroglial cells in murine cerebral cortex. Glia 4:138–148
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 131:3133–3145
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 10:1440–1448
Morshead CM, 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 12:249–256
Morshead CM, Reynolds BA, Craig CG, McBurney MW, Staines WA, 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 13:1071–1082
Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6:369–381
Ninkovic J, Gotz M (2007) Signaling in adult neurogenesis: from stem cell niche to neuronal networks. Curr Opin Neurobiol 17:338–344
Noctor SC, Martínez-Cerdeño V, Ivic L, Kriegstein AR (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7:136–144
Noctor SC, Martínez-Cerdeño V, Kriegstein AR (2008) Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J Comp Neurol 508:28–44
Nottebohm F (1985) Neuronal replacement in adulthood. Ann N Y Acad Sci 457:143–161
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
Nyfeler Y, Kirch RD, Mantei N, Leone DP, Radtke F, Suter U, Taylor V (2005) Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal. EMBO J 24:3504–3515
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 40:225–233
Ohnuma S, Harris WA (2003) Neurogenesis and the cell cycle. Neuron 40:199–208
Ohnuma S, Philpott A, Harris WA (2001) Cell cycle and cell fate in the nervous system. Curr Opin Neurobiol 11:66–73
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 18:2196–2207
Okano H (2002) Stem cell biology of the central nervous system. J Neurosci Res 69:698–707
Okano H, Sawamoto K (2008) Neural stem cells: involvement in adult neurogenesis and CNS repair. Philos Trans R Soc Lond B Biol Sci 363:2111–2122
Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257
Okano H, Sakaguchi M, Ohki K, Suzuki N, Sawamoto K (2007) Regeneration of the central nervous system using endogenous repair mechanisms. J Neurochem 102:1459–1465
Olson AK, Eadie BD, Ernst C, Christie BR (2006) Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus 16:250–260
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 26:1663–1672
Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494
Panchision DM (2009) The role of oxygen in regulating neural stem cells in development and disease. J Cell Physiol 220:562–568
Panchision DM, Pickel JM, Studer L, Lee SH, Turner PA, Hazel TG, McKay RD (2001) Sequential actions of BMP receptors control neural precursor cell production and fate. Genes Dev 15:2094–2110
Parr BA, Shea MJ, Vassileva G, McMahon AP (1993) Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development 119:247–261
Parras CM, Schuurmans C, Scardigli R, Kim J, Anderson DJ, Guillemot F (2002) Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity. Genes Dev 16:324–338
Perez SE, Rebelo S, Anderson DJ (1999) Early specification of sensory neuron fate revealed by expression and function of neurogenins in the chick embryo. Development 126:1715–1728
Pierani A, Brenner-Morton S, Chiang C, Jessell TM (1999) A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Cell 97:903–915
Pierani A, Moran-Rivard L, Sunshine MJ, Littman DR, Goulding M, Jessell TM (2001) Control of interneuron fate in the developing spinal cord by the progenitor homeodomain protein Dbx1. Neuron 29:367–384
Pilaz LJ, Patti D, Marcy G, Ollier E, Pfister S, Douglas RJ, 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 U S A 21:21924
Pistollato F, Chen HL, Schwartz PH, Basso G, Panchision DM (2007) Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes. Mol Cell Neurosci 35:424–435
Pollard SM, 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
Qian X, Shen Q, Goderie SK, He W, Capela A, Davis AA, 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
Raballo R, Rhee J, Lyn-Cook R, Leckman JF, Schwartz ML, Vaccarino FM (2000) Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J Neurosci 20:5012–5023
Ramon y Cajal S (1913) Degeneracion y regeneracion de los niervos. Imprenta de hijos de Nicolas Moya, Madrid
Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710
Reynolds BA, 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
Reynolds BA, Tetzlaff W, Weiss S (1992) A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci 12:4565–4574
Ringe J, Kaps C, Burmester GR, Sittinger M (2002) Stem cells for regenerative medicine: advances in the engineering of tissues and organs. Naturwissenschaften 89:338–351
Robertson KD, Wolffe AP (2000) DNA methylation in health and disease. Nat Rev Genet 1:11–19
Ross SE, Greenberg ME, Stiles CD (2003) Basic helix-loop-helix factors in cortical development. Neuron 39:13–25
Rottach A, Leonhardt H, Spada F (2009) DNA methylation-mediated epigenetic control. J Cell Biochem 108:43–51
Sanai N, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla A (2007) Comment on “Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension”. Science 318:393; author reply 393
Sansom SN, Griffiths DS, Faedo A, Kleinjan DJ, Ruan Y, Smith J, van Heyningen V, Rubenstein JL, Livesey FJ (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
Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE, Garcia AD, Sofroniew MV, Kandel ER, Santarelli L, Hen R, Drew MR (2006) Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci U S A 103:17501–17506
Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160
Seroogy KB, Gall CM, Lee DC, Kornblum HI (1995) Proliferative zones of postnatal rat brain express epidermal growth factor receptor mRNA. Brain Res 670:157–164
Shastri VP (2006) Future of regenerative medicine: challenges and hurdles. Artif Organs 30:828–834
Shen Q, Wang Y, Kokovay E, Lin G, Chuang SM, Goderie SK, 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
Shi Y, Massagué J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113:685–700
Shi Y, Sun G, Zhao C, Stewart R (2008) Neural stem cell self-renewal. Crit Rev Oncol Hematol 65:43–53
Shimogori T, Banuchi V, Ng HY, Strauss JB, Grove EA (2004) Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex. Development 131:5639–5647
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 U S A 96:5522–5527
Simpson TI, Price DJ (2002) Pax6; a pleiotropic player in development. Bioessays 24:1041–1051
Smirnova L, Gräfe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21:1469–1477
Stanfield BB, Trice JE (1988) Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections. Exp Brain Res 72:399–406
Steiner B, Wolf S, Kempermann G (2006) Adult neurogenesis and neurodegenerative disease. Regen Med 1:15–28
Storm EE, Garel S, Borello U, Hebert JM, Martinez S, McConnell SK, Martin GR, Rubenstein JL (2006) Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers. Development 133:1831–1844
Stoykova A, Fritsch R, Walther C, Gruss P (1996) Forebrain patterning defects in Small eye mutant mice. Development 122:3453–3465
Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45
Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, Cha KY, Chung HM, Yoon HS, Moon SY, Kim VN, Kim KS (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270:488–498
Suh H, Deng W, Gage FH (2009) Signaling in adult neurogenesis. Annu Rev Cell Dev Biol 25:253–275
Sun G, Yu RT, Evans RM, Shi Y (2007) Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc Natl Acad Sci U S A 104:15282–15287
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
Takahashi T, Nowakowski RS, Caviness VS (1995) The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J Neurosci 15:6046–6057
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 1:749–758
Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo JM, Doetsch F (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3:279–288
Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426
Toresson H, Potter SS, Campbell K (2000) Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2. Development 127:4361–4371
Turner BM (2002) Cellular memory and the histone code. Cell 111:285–291
Ulloa F, Briscoe J (2007) Morphogens and the control of cell proliferation and patterning in the spinal cord. Cell Cycle 6:2640–2649
Vaccarino FM, Schwartz ML, Raballo R, Nilsen J, Rhee J, Zhou M, Doetschman T, Coffin JD, Wyland JJ, Hung YT (1999a) Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat Neurosci 2:246–253
Vaccarino FM, Schwartz ML, 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
van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034
Vincent A, Van Seuningen I (2009) Epigenetics, stem cells and epithelial cell fate. Differentiation 78:99–107
Visvanathan J, Lee S, Lee B, Lee JW, Lee SK (2007) The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev 21:744–749
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 23:5919–5927
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
Wang Y, Yang J, Zheng H, Tomasek GJ, Zhang P, McKeever PE, Lee EY, 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 15:514–526
Warren N, Caric D, Pratt T, Clausen JA, Asavaritikrai P, Mason JO, Hill RE, Price DJ (1999) The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex. Cereb Cortex 9:627–635
Watanabe D, Suetake I, Tada T, Tajima S (2002) Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech Dev 118:187–190
Watanabe D, Uchiyama K, Hanaoka K (2006) Transition of mouse de novo methyltransferases expression from Dnmt3b to Dnmt3a during neural progenitor cell development. Neuroscience 142:727–737
Wenning GK, Odin P, Morrish P, Rehncrona S, Widner H, Brundin P, Rothwell JC, Brown R, Gustavii B, Hagell P, Jahanshahi M, Sawle G, Bjorklund A, Brooks DJ, Marsden CD, Quinn NP, Lindvall O (1997) Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson’s disease. Ann Neurol 42:95–107
Wine-Lee L, Ahn KJ, Richardson RD, Mishina Y, Lyons KM, Crenshaw EB (2004) Signaling through BMP type 1 receptors is required for development of interneuron cell types in the dorsal spinal cord. Development 131:5393–5403
Wolpert L (1969) Positional information and the spatial pattern of cellular differentiation. J Theor Biol 25:1–47
Yoon K, Nery S, Rutlin ML, 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 24:9497–9506
Zechner D, Fujita Y, Hülsken J, Müller T, Walther I, Taketo MM, Crenshaw EB, 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 258:406–418
Zhang ZG, Chopp M (2009) Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol 8:491–500
Zhang RL, Zhang ZG, Lu M, Wang Y, Yang JJ, 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 26:857–863
Zhang CL, Zou Y, He W, Gage FH, Evans RM (2008a) A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451:1004–1007
Zhang RL, Zhang ZG, Chopp M (2008b) Ischemic stroke and neurogenesis in the subventricular zone. Neuropharmacology 55:345–352
Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660
Zhu J, Zhou L, XingWu F (2006) Tracking neural stem cells in patients with brain trauma. N Engl J Med 355:2376–2378
Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5:311–322
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Arai, Y., Huttner, W.B., Calegari, F. (2016). Neural Stem Cells. In: Steinhoff, G. (eds) Regenerative Medicine - from Protocol to Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-27610-6_7
Download citation
DOI: https://doi.org/10.1007/978-3-319-27610-6_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-27608-3
Online ISBN: 978-3-319-27610-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)