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Neural Development and Stem Cells pp 61–80Cite as

The Cellular and Molecular Properties of Multipotent Neural Stem Cells

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Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

The promise of stem cell based therapies for the treatment of a number of debilitating neurological disorders has led to an increased interest in the mechanisms which regulate the development and maintenance of neural stem/progenitor cell populations. Here, we highlight some of the molecular and cellular similarities shared by neural stem and progenitor cell populations in both the developing and adult central nervous systems as well as differences that distinguish between them. Lastly, we discuss methods in which these properties can then be used to identify and isolate specific neural stem/progenitor cell populations from the CNS.

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References

  1. 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(6):707–715

    PubMed  CAS  Google Scholar 

  2. Duan X, Kang E, Liu CY, Ming GL, Song H (2008) Development of neural stem cell in the adult brain. Curr Opin Neurobiol 18(1):108–115

    PubMed  CAS  Google Scholar 

  3. Gil-Perotin S, Alvarez-Buylla A, Garcia-Verdugo JM (2009) Identification and characterization of neural progenitor cells in the adult mammalian brain. Adv Anat Embryol Cell Biol 203:1–101, ix

    Google Scholar 

  4. Weiss S, Dunne C, Hewson J, Wohl C, Wheatley M, Peterson AC, Reynolds BA (1996) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J Neurosci 16(23):7599–7609

    PubMed  CAS  Google Scholar 

  5. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255(5052):1707–1710

    PubMed  CAS  Google Scholar 

  6. Reynolds BA, Tetzlaff W, Weiss S (1992) A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci 12(11):4565–4574

    PubMed  CAS  Google Scholar 

  7. Davis AA, Temple S (1994) A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature 372(6503):263–266

    PubMed  CAS  Google Scholar 

  8. Merkle FT, Alvarez-Buylla A (2006) Neural stem cells in mammalian development. Curr Opin Cell Biol 18(6):704–709

    PubMed  CAS  Google Scholar 

  9. Pevny L, Rao MS (2003) The stem-cell menagerie. Trends Neurosci 26(7):351–359

    PubMed  CAS  Google Scholar 

  10. Arnold SJ, Robertson EJ (2009) Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nat Rev Mol Cell Biol 10(2):91–103

    PubMed  CAS  Google Scholar 

  11. Beddington RS (1994) Induction of a second neural axis by the mouse node. Development 120(3):613–620

    PubMed  CAS  Google Scholar 

  12. Rossant J, Tam PP (2009) Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse. Development 136(5):701–713

    PubMed  CAS  Google Scholar 

  13. Wilson SW, Houart C (2004) Early steps in the development of the forebrain. Dev Cell 6(2):167–181

    PubMed  CAS  Google Scholar 

  14. 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(9):3196–3201

    PubMed  CAS  Google Scholar 

  15. 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(13):3133–3145

    PubMed  CAS  Google Scholar 

  16. Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR (2001) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409(6821):714–720

    PubMed  CAS  Google Scholar 

  17. Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7(2):136–144

    PubMed  CAS  Google Scholar 

  18. Noctor SC, Martinez-Cerdeno V, Kriegstein AR (2008) Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J Comp Neurol 508(1):28–44

    PubMed  Google Scholar 

  19. 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(1):69–80

    PubMed  CAS  Google Scholar 

  20. Tropepe V, Hitoshi S, Sirard C, Mak TW, Rossant J, van der Kooy D (2001) Direct neural fate specification from embryonic stem cells: a primitive mammalian neural stem cell stage acquired through a default mechanism. Neuron 30(1):65–78

    PubMed  CAS  Google Scholar 

  21. Williams BP, Price J (1995) Evidence for multiple precursor cell types in the embryonic rat cerebral cortex. Neuron 14(6):1181–1188

    PubMed  CAS  Google Scholar 

  22. Kilpatrick TJ, Bartlett PF (1995) Cloned multipotential precursors from the mouse cerebrum require FGF-2, whereas glial restricted precursors are stimulated with either FGF-2 or EGF. J Neurosci 15(5 Pt 1):3653–3661

    PubMed  CAS  Google Scholar 

  23. Hack MA, Sugimori M, Lundberg C, Nakafuku M, Gotz M (2004) Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6. Mol Cell Neurosci 25(4):664–678

    PubMed  CAS  Google Scholar 

  24. Smukler SR, Runciman SB, Xu S, van der Kooy D (2006) Embryonic stem cells assume a primitive neural stem cell fate in the absence of extrinsic influences. J Cell Biol 172(1):79–90

    PubMed  CAS  Google Scholar 

  25. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27(3):275–280

    PubMed  CAS  Google Scholar 

  26. Boulder-Committee, Embryonic vertebrate central nervous system: revised terminology (1970). The Boulder Committee. Anat Rec 166(2):257–261

    Google Scholar 

  27. Alvarez-Buylla A, Garcia-Verdugo JM, Tramontin AD (2001) A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2(4):287–293

    PubMed  CAS  Google Scholar 

  28. Anthony TE, Klein C, Fishell G, Heintz N (2004) Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41(6):881–890

    PubMed  CAS  Google Scholar 

  29. Basak O, Taylor V (2007) Identification of self-replicating multipotent progenitors in the embryonic nervous system by high Notch activity and Hes5 expression. Eur J Neurosci 25(4):1006–1022

    PubMed  Google Scholar 

  30. Malatesta P, Appolloni I, Calzolari F (2008) Radial glia and neural stem cells. Cell Tissue Res 331(1):165–178

    PubMed  Google Scholar 

  31. Hartfuss E, Galli R, Heins N, Gotz M (2001) Characterization of CNS precursor subtypes and radial glia. Dev Biol 229(1):15–30

    PubMed  CAS  Google Scholar 

  32. Casper KB, McCarthy KD (2006) GFAP-positive progenitor cells produce neurons and oligodendrocytes throughout the CNS. Mol Cell Neurosci 31(4):676–684

    PubMed  CAS  Google Scholar 

  33. Gotz M, Barde YA (2005) Radial glial cells defined and major intermediates between embryonic stem cells and CNS neurons. Neuron 46(3):369–372

    PubMed  Google Scholar 

  34. Malatesta P, Hack MA, Hartfuss E, Kettenmann H, Klinkert W, Kirchhoff F, Gotz M (2003) Neuronal or glial progeny: regional differences in radial glia fate. Neuron 37(5):751–764

    PubMed  CAS  Google Scholar 

  35. Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker KL, Hack MA, Chapouton P, Barde YA, Gotz M (2002) Glial cells generate neurons: the role of the transcription factor Pax6. Nat Neurosci 5(4):308–315

    PubMed  CAS  Google Scholar 

  36. Luskin MB, Pearlman AL, Sanes JR (1988) Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a recombinant retrovirus. Neuron 1(8):635–647

    PubMed  CAS  Google Scholar 

  37. Walsh C, Cepko CL (1988) Clonally related cortical cells show several migration patterns. Science 241(4871):1342–1345

    PubMed  CAS  Google Scholar 

  38. McCarthy M, Turnbull DH, Walsh CA, Fishell G (2001) Telencephalic neural progenitors appear to be restricted to regional and glial fates before the onset of neurogenesis. J Neurosci 21(17):6772–6781

    PubMed  CAS  Google Scholar 

  39. 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(43):9497–9506

    PubMed  CAS  Google Scholar 

  40. Ciccolini F, Svendsen CN (1998) Fibroblast growth factor 2 (FGF-2) promotes acquisition of epidermal growth factor (EGF) responsiveness in mouse striatal precursor cells: identification of neural precursors responding to both EGF and FGF-2. J Neurosci 18(19):7869–7880

    PubMed  CAS  Google Scholar 

  41. Tropepe V, Sibilia M, Ciruna BG, Rossant J, Wagner EF, van der Kooy D (1999) Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev Biol 208(1):166–188

    PubMed  CAS  Google Scholar 

  42. Stancik EK, Navarro-Quiroga I, Sellke R, Haydar TF (2010) Heterogeneity in ventricular zone neural precursors contributes to neuronal fate diversity in the postnatal neocortex. J Neurosci 30(20):7028–7036

    PubMed  CAS  Google Scholar 

  43. Pontious A, Kowalczyk T, Englund C, Hevner RF (2008) Role of intermediate progenitor cells in cerebral cortex development. Dev Neurosci 30(1–3):24–32

    PubMed  CAS  Google Scholar 

  44. Englund C, Fink A, Lau C, Pham D, Daza RA, Bulfone A, Kowalczyk T, Hevner RF (2005) Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci 25(1):247–251

    PubMed  CAS  Google Scholar 

  45. Suh H, Deng W, Gage FH (2009) Signaling in Adult Neurogenesis. Annu Rev Cell Dev Biol 25:253–275

    PubMed  CAS  Google Scholar 

  46. Kempermann G, Wiskott L, Gage FH (2004) Functional significance of adult neurogenesis. Curr Opin Neurobiol 14(2):186–191

    PubMed  CAS  Google Scholar 

  47. Merkle FT, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A (2004) Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci U S A 101(50):17528–17532

    PubMed  CAS  Google Scholar 

  48. Doetsch F, Alvarez-Buylla A (1996) Network of tangential pathways for neuronal migration in adult mammalian brain. Proc Natl Acad Sci U S A 93(25):14895–14900

    PubMed  CAS  Google Scholar 

  49. Jankovski A, Sotelo C (1996) Subventricular zone-olfactory bulb migratory pathway in the adult mouse: cellular composition and specificity as determined by heterochronic and heterotopic transplantation. J Comp Neurol 371(3):376–396

    PubMed  CAS  Google Scholar 

  50. 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(13):5046–5061

    PubMed  CAS  Google Scholar 

  51. Lim DA, Fishell GJ, Alvarez-Buylla A (1997) Postnatal mouse subventricular zone neuronal precursors can migrate and differentiate within multiple levels of the developing neuraxis. Proc Natl Acad Sci U S A 94(26):14832–14836

    PubMed  CAS  Google Scholar 

  52. Levison SW, Goldman JE (1993) Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron 10(2):201–212

    PubMed  CAS  Google Scholar 

  53. Nait-Oumesmar B, Decker L, Lachapelle F, Avellana-Adalid V, Bachelin C, Van Evercooren AB (1999) Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur J Neurosci 11(12):4357–4366

    PubMed  CAS  Google Scholar 

  54. 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(1):25–34

    PubMed  CAS  Google Scholar 

  55. Johansson CB, Svensson M, Wallstedt L, Janson AM, Frisen J (1999) Neural stem cells in the adult human brain. Exp Cell Res 253(2):733–736

    PubMed  CAS  Google Scholar 

  56. 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(11):4462–4471

    PubMed  CAS  Google Scholar 

  57. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci U S A 96(20):11619–11624

    PubMed  CAS  Google Scholar 

  58. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97(6):703–716

    PubMed  CAS  Google Scholar 

  59. Doetsch F, Petreanu L, Caille I, Garcia-Verdugo JM, Alvarez-Buylla A (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36(6):1021–1034

    PubMed  CAS  Google Scholar 

  60. Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124(3):319–335

    PubMed  CAS  Google Scholar 

  61. 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(6):2027–2033

    PubMed  CAS  Google Scholar 

  62. Gage FH, Kempermann G, Palmer TD, Peterson DA, Ray J (1998) Multipotent progenitor cells in the adult dentate gyrus. J Neurobiol 36(2):249–266

    PubMed  CAS  Google Scholar 

  63. Marmur R, Mabie PC, Gokhan S, Song Q, Kessler JA, Mehler MF (1998) Isolation and developmental characterization of cerebral cortical multipotent progenitors. Dev Biol 204(2):577–591

    PubMed  CAS  Google Scholar 

  64. Shihabuddin LS, Horner PJ, Ray J, Gage FH (2000) Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci 20(23):8727–8735

    PubMed  CAS  Google Scholar 

  65. Cameron HA, McKay R (1998) Stem cells and neurogenesis in the adult brain. Curr Opin Neurobiol 8(5):677–680

    PubMed  CAS  Google Scholar 

  66. Palmer TD, Markakis EA, Willhoite AR, Safar F, Gage FH (1999) Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS. J Neurosci 19(19):8487–8497

    PubMed  CAS  Google Scholar 

  67. Stanfield BB, Trice JE (1988) Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections. Exp Brain Res 72(2):399–406

    PubMed  CAS  Google Scholar 

  68. Markakis EA, Palmer TD, Randolph-Moore L, Rakic P, Gage FH (2004) Novel neuronal phenotypes from neural progenitor cells. J Neurosci 24(12):2886–2897

    PubMed  CAS  Google Scholar 

  69. Carlen M, Cassidy RM, Brismar H, Smith GA, Enquist LW, Frisen J (2002) Functional integration of adult-born neurons. Curr Biol 12(7):606–608

    PubMed  CAS  Google Scholar 

  70. Feng R, Rampon C, Tang YP, Shrom D, Jin J, Kyin M, Sopher B, Miller MW, Ware CB, Martin GM, Kim SH, Langdon RB, Sisodia SS, Tsien JZ (2001) Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron 32(5):911–926

    PubMed  CAS  Google Scholar 

  71. Macklis JD (2001) Neurobiology: New memories from new neurons. Nature 410(6826): 314-5, 317.

    Google Scholar 

  72. Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410(6826):372–376

    PubMed  CAS  Google Scholar 

  73. Gould E, Gross CG (2002) Neurogenesis in adult mammals: some progress and problems. J Neurosci 22(3):619–623

    PubMed  CAS  Google Scholar 

  74. Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386(6624):493–495

    PubMed  CAS  Google Scholar 

  75. Kempermann G, Gage FH (2002) Genetic determinants of adult hippocampal neurogenesis correlate with acquisition, but not probe trial performance, in the water maze task. Eur J Neurosci 16(1):129–136

    PubMed  CAS  Google Scholar 

  76. Kokaia Z, Lindvall O (2003) Neurogenesis after ischaemic brain insults. Curr Opin Neurobiol 13(1):127–132

    PubMed  CAS  Google Scholar 

  77. Jessell TM (2000) Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 1(1):20–29

    PubMed  CAS  Google Scholar 

  78. Lumsden A, Krumlauf R (1996) Patterning the vertebrate neuraxis. Science 274(5290):1109–1115

    PubMed  CAS  Google Scholar 

  79. Wilson SW, Rubenstein JL (2000) Induction and dorsoventral patterning of the telencephalon. Neuron 28(3):641–651

    PubMed  CAS  Google Scholar 

  80. 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(4):435–445

    PubMed  CAS  Google Scholar 

  81. Hitoshi S, Tropepe V, Ekker M, van der Kooy D (2002) Neural stem cell lineages are regionally specified, but not committed, within distinct compartments of the developing brain. Development 129(1):233–244

    PubMed  CAS  Google Scholar 

  82. Nakagawa Y, Kaneko T, Ogura T, Suzuki T, Torii M, Kaibuchi K, Arai K, Nakamura S, Nakafuku M (1996) Roles of cell-autonomous mechanisms for differential expression of region-specific transcription factors in neuroepithelial cells. Development 122(8):2449–2464

    PubMed  CAS  Google Scholar 

  83. Zappone MV, Galli R, Catena R, Meani N, De Biasi S, Mattei E, Tiveron C, Vescovi AL, Lovell-Badge R, Ottolenghi S, Nicolis SK (2000) Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. Development 127(11):2367–2382

    PubMed  CAS  Google Scholar 

  84. McConnell SK, Kaznowski CE (1991) Cell cycle dependence of laminar determination in developing neocortex. Science 254(5029):282–285

    PubMed  CAS  Google Scholar 

  85. Anderson DJ, Gage FH, Weissman IL (2001) Can stem cells cross lineage boundaries? Nat Med 7(4):393–395

    PubMed  CAS  Google Scholar 

  86. Edlund T, Jessell TM (1999) Progression from extrinsic to intrinsic signaling in cell fate specification: a view from the nervous system. Cell 96(2):211–224

    PubMed  CAS  Google Scholar 

  87. Gabay L, Lowell S, Rubin LL, Anderson DJ (2003) Deregulation of dorsoventral patterning by FGF confers trilineage differentiation capacity on CNS stem cells in vitro. Neuron 40(3):485–499

    PubMed  CAS  Google Scholar 

  88. Leber SM, Breedlove SM, Sanes JR (1990) Lineage, arrangement, and death of clonally related motoneurons in chick spinal cord. J Neurosci 10(7):2451–2462

    PubMed  CAS  Google Scholar 

  89. Luskin MB, Parnavelas JG, Barfield JA (1993) Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells. J Neurosci 13(4):1730–1750

    PubMed  CAS  Google Scholar 

  90. Deleyrolle LP, Reynolds BA (2009) Isolation, expansion, and differentiation of adult Mammalian neural stem and progenitor cells using the neurosphere assay. Methods Mol Biol 549:91–101

    PubMed  CAS  Google Scholar 

  91. Jensen JB, Parmar M (2006) Strengths and limitations of the neurosphere culture system. Mol Neurobiol 34(3):153–161

    PubMed  CAS  Google Scholar 

  92. Kondo T, Raff M (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289(5485):1754–1757

    PubMed  CAS  Google Scholar 

  93. Brewer GJ (1999) Regeneration and proliferation of embryonic and adult rat hippocampal neurons in culture. Exp Neurol 159(1):237–247

    PubMed  CAS  Google Scholar 

  94. Ahn S, Joyner AL (2005) In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog. Nature 437(7060):894–897

    PubMed  CAS  Google Scholar 

  95. Gage FH (2000) Mammalian neural stem cells. Science 287(5457):1433–1438

    PubMed  CAS  Google Scholar 

  96. Brustle O, McKay RD (1995) The neuroepithelial stem cell concept: implications for neuro-oncology. J Neurooncol 24(1):57–59

    PubMed  CAS  Google Scholar 

  97. Campbell K, Olsson M, Bjorklund A (1995) Regional incorporation and site-specific differentiation of striatal precursors transplanted to the embryonic forebrain ventricle. Neuron 15(6):1259–1273

    PubMed  CAS  Google Scholar 

  98. Fishell G (1995) Striatal precursors adopt cortical identities in response to local cues. Development 121(3):803–812

    PubMed  CAS  Google Scholar 

  99. Vicario-Abejon C, Cunningham MG, McKay RD (1995) Cerebellar precursors transplanted to the neonatal dentate gyrus express features characteristic of hippocampal neurons. J Neurosci 15(10):6351–6363

    PubMed  CAS  Google Scholar 

  100. Gage FH, Ray J, Fisher LJ (1995) Isolation, characterization, and use of stem cells from the CNS. Annu Rev Neurosci 18:159–192

    PubMed  CAS  Google Scholar 

  101. Takahashi M, Palmer TD, Takahashi J, Gage FH (1998) Widespread integration and survival of adult-derived neural progenitor cells in the developing optic retina. Mol Cell Neurosci 12(6):340–348

    PubMed  CAS  Google Scholar 

  102. Frederiksen K, McKay RD (1988) Proliferation and differentiation of rat neuroepithelial precursor cells in vivo. J Neurosci 8(4):1144–1151

    PubMed  CAS  Google Scholar 

  103. Lendahl U, Zimmerman LB, McKay R (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595

    PubMed  CAS  Google Scholar 

  104. Pevny LH, Sockanathan S, Placzek M, Lovell-Badge R (1998) A role for SOX1 in neural determination. Development 125(10):1967–1978

    PubMed  CAS  Google Scholar 

  105. Sakakibara S, Imai T, Hamaguchi K, Okabe M, Aruga J, Nakajima K, Yasutomi D, Nagata T, Kurihara Y, Uesugi S, Miyata T, Ogawa M, Mikoshiba K, Okano H (1996) Mouse-Musashi-1, a neural RNA-binding protein highly enriched in the mammalian CNS stem cell. Dev Biol 176(2):230–242

    PubMed  CAS  Google Scholar 

  106. Weinmaster G, Roberts VJ, Lemke G (1991) A homolog of Drosophila Notch expressed during mammalian development. Development 113(1):199–205

    PubMed  CAS  Google Scholar 

  107. Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28(3):713–726

    PubMed  CAS  Google Scholar 

  108. Pevny L, Placzek M (2005) SOX genes and neural progenitor identity. Curr Opin Neurobiol 15(1):7–13

    PubMed  CAS  Google Scholar 

  109. Kalani MYS, Cheshier SH, Cord BJ, Bababeygy SR, Vogel H, Weissman IL, Palmer TD, Nusse R (2008) Wnt-mediated self-renewal of neural stem/progenitor cells. Proc Nat Acad Sci 105(44):16970–16975

    PubMed  CAS  Google Scholar 

  110. Lathia JD, Mattson MP, Cheng A (2008) Notch: from neural development to neurological disorders. J Neurochem 107(6):1471–1481

    PubMed  CAS  Google Scholar 

  111. Shi Y, Chichung Lie D, Taupin P, Nakashima K, Ray J, Yu RT, Gage FH, Evans RM (2004) Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature 427(6969): 78-83

    Google Scholar 

  112. Sakakibara S, Nakamura Y, Yoshida T, Shibata S, Koike M, Takano H, Ueda S, Uchiyama Y, Noda T, Okano H (2002) RNA-binding protein Musashi family: roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation. Proc Natl Acad Sci U S A 99(23):15194–15199

    PubMed  CAS  Google Scholar 

  113. Bylund M, Andersson E, Novitch BG, Muhr J (2003) Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat Neurosci 6(11):1162–1168

    PubMed  CAS  Google Scholar 

  114. Graham V, Khudyakov J, Ellis P, Pevny L (2003) SOX2 functions to maintain neural progenitor identity. Neuron 39(5):749–765

    PubMed  CAS  Google Scholar 

  115. Chambers CB, Peng Y, Nguyen H, Gaiano N, Fishell G, Nye JS (2001) Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors. Development 128(5):689–702

    PubMed  CAS  Google Scholar 

  116. Gaiano N, Fishell G (2002) The role of notch in promoting glial and neural stem cell fates. Annu Rev Neurosci 25:471–490

    PubMed  CAS  Google Scholar 

  117. Gaiano N, Nye JS, Fishell G (2000) Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26(2):395–404

    PubMed  CAS  Google Scholar 

  118. Ishibashi M, Moriyoshi K, Sasai Y, Shiota K, Nakanishi S, Kageyama R (1994) Persistent expression of helix-loop-helix factor HES-1 prevents mammalian neural differentiation in the central nervous system. EMBO J 13(8):1799–1805

    PubMed  CAS  Google Scholar 

  119. Ishibashi M, Ang SL, Shiota K, Nakanishi S, Kageyama R, Guillemot F (1995) Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects. Genes Dev 9(24):3136–3148

    PubMed  CAS  Google Scholar 

  120. Furukawa T, Morrow EM, Cepko CL (1997) Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation. Cell 91(4):531–541

    PubMed  CAS  Google Scholar 

  121. Akita J, Takahashi M, Hojo M, Nishida A, Haruta M, Honda Y (2002) Neuronal differentiation of adult rat hippocampus-derived neural stem cells transplanted into embryonic rat explanted retinas with retinoic acid pretreatment. Brain Res 954(2):286–293

    PubMed  CAS  Google Scholar 

  122. Scheer N, Groth A, Hans S, Campos-Ortega JA (2001) An instructive function for Notch in promoting gliogenesis in the zebrafish retina. Development 128(7):1099–1107

    PubMed  CAS  Google Scholar 

  123. Park IK, Morrison SJ, Clarke MF (2004) Bmi1, stem cells, and senescence regulation. J Clin Invest 113(2):175–179

    PubMed  CAS  Google Scholar 

  124. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425(6961):962–967

    PubMed  CAS  Google Scholar 

  125. Ezoe S, Matsumura I, Satoh Y, Tanaka H, Kanakura Y (2004) Cell cycle regulation in hematopoietic stem/progenitor cells. Cell Cycle 3(3):314–318

    PubMed  CAS  Google Scholar 

  126. Raaphorst FM (2003) Self-renewal of hematopoietic and leukemic stem cells: a central role for the Polycomb-group gene Bmi-1. Trends Immunol 24(10):522–524

    PubMed  CAS  Google Scholar 

  127. Akasaka T, Tsuji K, Kawahira H, Kanno M, Harigaya K, Hu L, Ebihara Y, Nakahata T, Tetsu O, Taniguchi M, Koseki H (1997) The role of mel-18, a mammalian Polycomb group gene, during IL-7-dependent proliferation of lymphocyte precursors. Immunity 7(1):135–146

    PubMed  CAS  Google Scholar 

  128. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR (2002) A stem cell molecular signature. Science 298(5593):601–604

    PubMed  CAS  Google Scholar 

  129. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science 298(5593):597–600

    PubMed  CAS  Google Scholar 

  130. Terskikh AV, Easterday MC, Li L, Hood L, Kornblum HI, Geschwind DH, Weissman IL (2001) From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci U S A 98(14):7934–7939

    PubMed  CAS  Google Scholar 

  131. Geschwind DH, Ou J, Easterday MC, Dougherty JD, Jackson RL, Chen Z, Antoine H, Terskikh A, Weissman IL, Nelson SF, Kornblum HI (2001) A genetic analysis of neural progenitor differentiation. Neuron 29(2):325–339

    PubMed  CAS  Google Scholar 

  132. D’Amour KA, Gage FH (2003) Genetic and functional differences between multipotent neural and pluripotent embryonic stem cells. Proc Natl Acad Sci U S A 100(Suppl 1):11866–11872

    PubMed  Google Scholar 

  133. Shoemaker LD, Orozco NM, Geschwind DH, Whitelegge JP, Faull KF, Kornblum HI (2010) Identification of differentially expressed proteins in murine embryonic and postnatal cortical neural progenitors. PLoS One5(2):e9121

    PubMed  Google Scholar 

  134. Krol J, Loedige I, Filipowicz W The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610

    Google Scholar 

  135. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12(9):735–739

    PubMed  CAS  Google Scholar 

  136. Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific MicroRNAs. Dev Cell 5(2):351–358

    PubMed  CAS  Google Scholar 

  137. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9(10):1274–1281

    PubMed  CAS  Google Scholar 

  138. Miska EA, Alvarez-Saavedra E, Townsend M, Yoshii A, Sestan N, Rakic P, Constantine-Paton M, Horvitz HR (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5(9):R68

    PubMed  Google Scholar 

  139. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5(3):R13

    PubMed  Google Scholar 

  140. Andersson T, Rahman S, Sansom SN, Alsià JM, Kaneda M, Smith J, O’Carroll D, Tarakhovsky A, Livesey FJ (2010) Reversible Block of Mouse Neural Stem Cell Differentiation in the Absence of Dicer and MicroRNAs. PLoS ONE 5(10):13453

    Google Scholar 

  141. Zhao C, Sun G, Li S, Lang MF, Yang S, Li W, Shi Y (2010) MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling. Proc Natl Acad Sci U S A 107(5):1876–1881

    PubMed  CAS  Google Scholar 

  142. Zhao C, Sun G, Li S, Shi Y (2009) A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. Nat Struct Mol Biol 16(4):365–371

    PubMed  CAS  Google Scholar 

  143. Gaughwin P, Ciesla M, Yang H, Lim B, Brundin P (2011) Stage-Specific Modulation of Cortical Neuronal Development by Mmu-miR-134. Cereb Cortex 21(8):1857–1869

    PubMed  Google Scholar 

  144. Nielsen JA, Lau P, Maric D, Barker JL, Hudson LD (2009) Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis. BMC Neurosci 10:98

    PubMed  Google Scholar 

  145. Cai J, Wu Y, Mirua T, Pierce JL, Lucero MT, Albertine KH, Spangrude GJ, Rao MS (2002) Properties of a fetal multipotent neural stem cell (NEP cell). Dev Biol 251(2):221–240

    PubMed  CAS  Google Scholar 

  146. Rao MS (1999) Multipotent and restricted precursors in the central nervous system. Anat Rec 257(4):137–148

    PubMed  CAS  Google Scholar 

  147. Maric D, Maric I, Chang YH, Barker JL (2003) Prospective cell sorting of embryonic rat neural stem cells and neuronal and glial progenitors reveals selective effects of basic fibroblast growth factor and epidermal growth factor on self-renewal and differentiation. J Neurosci 23(1):240–251

    PubMed  CAS  Google Scholar 

  148. Bartlett PF, Brooker GJ, Faux CH, Dutton R, Murphy M, Turnley A, Kilpatrick TJ (1998) Regulation of neural stem cell differentiation in the forebrain. Immunol Cell Biol 76(5):414–418

    PubMed  CAS  Google Scholar 

  149. Capela A, Temple S (2002) LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron 35(5):865–875

    PubMed  Google Scholar 

  150. Corti S, Nizzardo M, Nardini M, Donadoni C, Locatelli F, Papadimitriou D, Salani S, Del Bo R, Ghezzi S, Strazzer S, Bresolin N, Comi GP (2007) Isolation and characterization of murine neural stem/progenitor cells based on Prominin-1 expression. Exp Neurol 205(2):547–562

    PubMed  CAS  Google Scholar 

  151. Lee A, Kessler JD, Read TA, Kaiser C, Corbeil D, Huttner WB, Johnson JE, Wechsler-Reya RJ (2005) Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci 8(6):723–729

    PubMed  CAS  Google Scholar 

  152. Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A 97(26):14720–14725

    PubMed  CAS  Google Scholar 

  153. Sun Y, Kong W, Falk A, Hu J, Zhou L, Pollard S, Smith A (2009) CD133 (Prominin) negative human neural stem cells are clonogenic and tripotent. PLoS One 4(5):e5498

    PubMed  Google Scholar 

  154. Yamaguchi M, Saito H, Suzuki M, Mori K (2000) Visualization of neurogenesis in the central nervous system using nestin promoter-GFP transgenic mice. NeuroReport 11(9):1991–1996

    PubMed  CAS  Google Scholar 

  155. Roy NS, Benraiss A, Wang S, Fraser RA, Goodman R, Couldwell WT, Nedergaard M, Kawaguchi A, Okano H, Goldman SA (2000) Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone. J Neurosci Res 59(3):321–331

    PubMed  CAS  Google Scholar 

  156. Sawamoto K, Nakao N, Kakishita K, Ogawa Y, Toyama Y, Yamamoto A, Yamaguchi M, Mori K, Goldman SA, Itakura T, Okano H (2001) Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene. J Neurosci 21(11):3895–3903

    PubMed  CAS  Google Scholar 

  157. Mignone JL, Kukekov V, Chiang AS, Steindler D, Enikolopov G (2004) Neural stem and progenitor cells in nestin-GFP transgenic mice. J Comp Neurol 469(3):311–324

    PubMed  CAS  Google Scholar 

  158. Ellis P, Fagan BM, Magness ST, Hutton S, Taranova O, Hayashi S, McMahon A, Rao M, Pevny L (2004) SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult. Dev Neurosci 26(2–4):148–165

    PubMed  CAS  Google Scholar 

  159. Aubert J, Stavridis MP, Tweedie S, O’Reilly M, Vierlinger K, Li M, Ghazal P, Pratt T, Mason JO, Roy D, Smith A (2003) Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knock-in mice. Proc Natl Acad Sci U S A 100(Suppl 1):11836–11841

    PubMed  CAS  Google Scholar 

  160. Rizzoti K, Brunelli S, Carmignac D, Thomas PQ, Robinson IC, Lovell-Badge R (2004) SOX3 is required during the formation of the hypothalamo-pituitary axis. Nat Genet 36:246–255

    Google Scholar 

  161. Li M, Pevny L, Lovell-Badge R, Smith A (1998) Generation of purified neural precursors from embryonic stem cells by lineage selection. Curr Biol 8(17):971–974

    PubMed  CAS  Google Scholar 

  162. Hutton SR, Pevny LH (2011) SOX2 expression levels distinguish between neural progenitor populations of the developing dorsal telencephalon. Dev Biol 352(1):40–47

    PubMed  CAS  Google Scholar 

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  1. Department of Genetics and UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA

    Scott R. Hutton & Larysa H. Pevny

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    Mohan C. Vemuri

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Hutton, S.R., Pevny, L.H. (2012). The Cellular and Molecular Properties of Multipotent Neural Stem Cells. In: Rao, M., Carpenter, M., Vemuri, M. (eds) Neural Development and Stem Cells. Stem Cell Biology and Regenerative Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3801-4_3

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