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Vol. 22, No. 1-2, 2000
Issue release date: January–April (February 2000)
Dev Neurosci 2000;22:139–153

Musashi1: An Evolutionally Conserved Marker for CNS Progenitor Cells Including Neural Stem Cells

Kaneko Y. · Sakakibara S. · Imai T. · Suzuki A. · Nakamura Y. · Sawamoto K. · Ogawa Y. · Toyama Y. · Miyata T. · Okano H.
aDivision of Neuroanatomy, Department of Neuroscience, Biomedical Research Center, Osaka University Graduate School of Medicine; bDepartment of Anatomy, Institute of Basic Medical Sciences, University of Tsukuba; cCore Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), and dDepartment of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan

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In situ detection of neural progenitor cells including stem-like cells is essential for studying the basic mechanisms of the generation of cellular diversity in the CNS, upon which therapeutic treatments for CNS injuries, degenerative diseases, and brain tumors may be based. We have generated rat monoclonal antibodies (Mab 14H1 and 14B8) that recognize an RNA-binding protein Musashi1, but not a Musashi1-related protein, Musashi2. The amino acid sequences at the epitope sites of these anti-Musashi1 Mabs are remarkably conserved among the human, mouse, and Xenopus proteins. Spatiotemporal patterns of Musashi1 immunoreactivity in the developing and/or adult CNS tissues of frogs, birds, rodents, and humans indicated that our anti-Musashi1 Mabs reacted with undifferentiated, proliferative cells in the CNS of all the vertebrates tested. Double or triple immunostaining of embryonic mouse brain cells in monolayer cultures demonstrated strong Musashi1 expression in Nestin(+)/RC2(+) cells. The relative number of Musashi1(+)/Nestin(+)/RC2(+) cells increased fivefold when embryonic forebrain cells were cultured to form ‘neurospheres’ in which stem-like cells are known to be enriched through their self-renewing mode of growth. Nestin(+)/RC2(–) cells, which included Tα1-GFP(+) neuronal progenitor cells and GLAST(+) astroglial precursor cells, were also Musashi1(+), as were GFAP(+) astrocytes. Young neurons showed a trace of Musashi1 expression. Cells committed to the oligodendroglial lineage were Musashi(–). Musashi1 was localized to the perikarya of CNS stem-like cells and non-oligodendroglial progenitor cells without shifting to cell processes or endfeet, and is therefore advantageous for identifying each cell and counting cells in situ.

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  1. Sakakibara S, Imai T, 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 176:230–242.
  2. Nakamura M, Okano H, Blendy J, Montell C (1994): MUSASHI, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron 13:67–81.
  3. Sakakibara S, Okano H (1997): Expression of neural RNA-binding proteins in the postnatal CNS: Implication of their roles in neural and glial cell development. J Neurosci 17:8300–8312.
  4. Maeda N, Niinobe M, Nakahira K, Mikoshiba K (1988): Purification and characterization of P400 protein, a glycoprotein characteristic of Purkinje cell, from mouse cerebellum. J Neurochem 51:1724–1730.
  5. Yelton DE, Diamond BA, Kwan SP, Scharff MD (1978): Fusion of mouse myeloma and spleen cells. Curr Top Microbiol Immunol 81:1–7.
  6. Mayor HD, Hampton JC, Rosario B (1961): A simple method for removing the resin from epoxy embedding tissue. J Cell Biol 9:909–910.
  7. Marusich MF, Furneaux HM, Henion PD, Weston JA (1994): Hu neuronal proteins are expressed in proliferating neurogenic cells. J Neurobiol 25:143–155.
  8. Hockfield S, McKay R (1985): Identification of major cell classes in the developing mammalian nervous system. J Neurosci 5:3310–3328.
  9. Frederiksen K, McKay RD (1988): Proliferation and differentiation of rat neuroepithelial precursor cells in vivo. J Neurosci 8:1144–1151.
  10. Lendahl U, Zimmerman LB, McKay RDG (1990): CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595.
  11. Misson JP, Edwards MA, Yamamoto M, Caviness VS Jr (1988): Identification of radial glial cells within the developing murine central nervous system: Studies based upon a new immunohistochemical marker. Dev Brain Res 44:95–108.
  12. Shibata T, Yamada K, Watanabe M, Ikenaka K, Wada K, Tanaka K, Inoue Y (1997): Glutamate transporter GLAST is expressed in the radial glia-astrocyte lineage of developing mouse spinal cord. J Neurosci 179212–9219.
  13. Goldman JE, Hirano M, Yu RK, Seyfried TN (1984): GD3 ganglioside is a glycolipid characteristic of immature neuroectodermal cells. J Neuroimmunol 7:179–192.
  14. Vaysse PJ, Goldman, JE (1990): A clonal analysis of glial lineages in neonatal forebrain development in vitro. Neuron 5:227–235.
  15. Niinobe M, Maeda N, Ino H, Mikoshiba K (1988): Characterization of microtubule-associated protein 2 from mouse brain and its localization in the cerebellar cortex. J Neurochem 51:1132–1139.
  16. Reynolds BA, Weiss S (1992): Generation of neurons and astrocytes from isolated cells of adult mammalian central nervous system. Science 255:1707–1710.
  17. Reynolds BA, Tetzlaff W, Weiss S (1992): A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci 12:4565–4574.
  18. 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.
  19. Gritti A, Parati EA, Cova L, Frolichsthal P, Galli R, Wanke E, Faravelli L, Morassutti DJ, Roisen F, Nickel DD, Vescovi AL (1996): Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor. J Neurosci 16:1091–1100.
  20. Svendsen CN, ter Borg MG, Armstrong RJ, Rosser AE, Chandran S, Ostenfeld T, Caldwell MA (1998): A new method for the rapid and long-term growth of human neural precursor cells. J Neurosci Methods 85:141–52.
  21. Vescovi AL, Parati EA, Gritti A, Poulin P, Ferrario M, Wanke E, Frolichsthal-Schoeller P, Cova L, Arcellana-Panlilio M, Colombo A, Galli R (1999): Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol 156:71–83.
  22. Good PJ, Rebbert ML, Dawid IB (1993): Three new members of the RNP protein family in Xenopus. Nucl Acid Res 21:999–1006.
  23. Good P, Yoda A, Sakakibara S, Yamamoto A, Imai T, Sawa H, Ikeuchi, T, Tsuji S, Satoh H, Okano H (1998): The human Musashi homolog1 (MSI1) gene encoding the homologue of Musashi/Nrp-1, a neural RNA-binding protein putatively expressed in CNS stem cells and neural progenitor cells. Genomics 52:382–384.
  24. Richter K, Good PJ, Dawid IB (1990): A developmentally regulated, nervous system-specific gene in Xenopus encodes a putative RNA-binding protein. New Biol 2:556–565.
  25. Barami K, Iversen K, Furneaux H, Goldman SA (1995): Early expression of Hu proteins by newly generated neurons of the adult avian forebrain. J Neurobiol 28:82–101.
  26. Altman C (1972): Postnatal development of the cerebellar cortex in the rat. I. The external germinal layer and the transitional molecular layer. J Comp Neurol 145:353–398.
  27. Altman JC (1969): Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137:433–458.
  28. 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 90:2074–2077.
  29. Luskin MB (1993): Restricted proliferation and migration of postnatally generated neurons derived from forebrain subventricular zone. Neuron 11:173–189.
  30. Lois C, Alvarez-Buylla A (1994): Long-distance neuronal migration in the adult mammalian brain. Science 264:1145–1148.
  31. 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.
  32. Kirchenbaum B, Goldman S (1995): BDNF promotes the survival of neurons arising from the adult rat forebrain subependymal zone. Proc Natl Acad Sci USA 92:210–214.
  33. Doetsch F, Alvarez-Buylla A (1996): Network of tangential pathways for neuronal migration in adult mammalian brain. Proc Natl Acad Sci USA 93:14895–14900.
  34. 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.
  35. Kempermann G, Kuhn HG, Gage FH (1997): Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc Natl Acad Sci USA 94:10409–10414.
  36. Gage FH, Kempermann G, Palmer TD, Peterson DA, Ray J (1998): Multipotential progenitor cells in the adult dentate gyrus. J Neurobiol 2:249–266.
  37. Lee MK, Tuttle JB, Rebhum LL, Cleveland DW, Frankfurter A (1990): The expression and posttranslational modification of a neuron-specific β-tubulin isotype during chick embryogenesis. Cell Motil Cytoskel 17:118–132.
  38. Menezes JRL, Luskin MB (1994): Expression of neuron-specific tubulin defines a novel population in the proliferative layers of the developing telencephalon. J Neurosci 14:5399–5416.
  39. Wang S, Wu H, Jiang J, Delohery TM, Isdell F, Goldman SA (1998): Isolation of neuronal precursors by sorting embryonic forebrain transfected with GFP regulated by the Tα1 tubulin promotor. Nat Biotech 16:196–201.
  40. Sawamoto K, Ogawa Y, Saiwaki T, Kawaguchi A, Miyata T, Goldman SA, Okano H (1999): Isolation of neuronal precursor cells by FACS from the Tα1-GFP transgenic animals. Soc Neurosci Abstr.
  41. Pincus DW, Keyoung H, Restelli C, Goodman RR, Fraser RAR, Edgar M, Sakakibara S, Okano H, Nedergaard M, Goldman, SA (1998): FGF2/BDNF-responsive neuronal progenitor cells in the adult human subependyma. Ann Neurol 43:576–585.
  42. 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.
  43. 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 97:703–716.
  44. 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.
  45. Barres BA (1999): A new role for glia: Generation of neurons! Cell 97:667–670.
  46. Sotelo C, Alvarado-Mallart RM, Frain M, Vernet M (1994): Molecular plasticity of adult Bergmann fibers is associated with radial migration of grafted Purkinje cells. J Neurosci 14:124–133.
  47. Hunter KE, Hatten ME (1995): Radial glial cell transformation to astrocytes is bidirectional: Regulation by a diffusible factor in embryonic forebrain. Proc Natl Acad Sci USA 92:2061–2065.
  48. Soriano E, Alvarado-Mallart RM, Dumesnil N, Del Rio JA, Sotelo C (1997): Cajal-Retzius cells regulate the radial glia phenotype in the adult and developing cerebellum and alter granule cell migration. Neuron 18:563–577.
  49. Pincus DW, Goodman RG, Goldman SA (1998): Neural stem cells: A strategy for gene therapy and brain repair. Neurosurgery 42:858–867.
  50. Leonard RB, Coggeshall RE, Willis WD (1978): A documentation of an age-related increase in neuronal and axonal numbers in the stingray, Dasyatis sabina, Leseuer. J Comp Neurol 179:13–21.
  51. Lopez-Garcia C, Molowny A, Garcia-Verdugo JM, Ferrer I (1988): Delayed postnatal neurogenesis in the cerebral cortex of lizards. Brain Res 471:167–174.
  52. Stone LS (1950): Neural retinal degeneration followed by regeneration from surviving retinal pigment cells in grafted adult salamander eyes. Anat Rec 106:89–109.
  53. Hitchcock PF, Raymond PA (1992): Retinal regeneration. Trends Neurosci 15:103–108.
  54. Goldman SA, Nottebohm F (1983): Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci USA 80:2390–2394.
  55. Alvarez-Buylla A, Kirn JR, Nottebohm F (1990): Birth of projection neurons in adult avian brain may be related to perceptual or motor learning. Science 249:1444–1447.
  56. Goldman S, Zukhar A, Barami K, Mikawa T, Niedzwiecki D (1996): Ependymal/subependymal zone cells of the postnatal and adult songbird brain generate both neurons and non-neuronal siblings, in vitro and in vivo. J Neurobiol 30:505–520.
  57. Goldman SA (1998): Adult neurogenesis: From canaries to the clinic. J Neurobiol 4:1313–1317.
  58. 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.
  59. Kadin ME, Rubinstein LJ, Nelson JS (1970): Neonatal cerebellar medulloblastoma originating from the fetal external granular layer. J Neuropathol Exp Neurol 29:583–600.

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