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Vol. 28, No. 1-2, 2006
Issue release date: February 2006
Dev Neurosci 2006;28:81–91

Notch Signaling in Astrocytes and Neuroblasts of the Adult Subventricular Zone in Health and after Cortical Injury

Givogri M.I. · de Planell M. · Galbiati F. · Superchi D. · Gritti A. · Vescovi A. · de Vellis J. · Bongarzone E.R.
aLaboratory for Gene Therapy of Neurodegenerative Disorders, San Raffaele Telethon Institute for Gene Therapy, and bStem Cell Research Institute, San Raffaele Scientific Institute, Milan, Italy; cNeurobiology Group, Mental Retardation Research Center, University of California, Los Angeles, Calif., USA

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The postnatal subventricular zone (SVZ) is a niche for continuous neurogenesis in the adult brain and likely plays a fundamental role in self-repair responses in neurodegenerative conditions. Maintenance of the pool of neural stem cells within this area depends on cell-cell communication such as that provided by the Notch signaling pathway. Notch1 receptor mRNA has been found distributed in different areas of the postnatal brain including the SVZ. Although the identity of Notch1-expressing cells has been established in the majority of these areas, it is still unclear what cell types within the SVZ are expressing components of this pathway. Here we demonstrate that most of expression of Notch1 in the adult SVZ occurs in polysialylated neural cell adhesion molecule (PSA-NCAM)-positive neural precursors and in glial fibrillary acidic protein-positive SVZ astrocytes. Notch1 was also found in PSA-NCAM-positive neuroblasts located within the rostral migratory stream (RMS) but much less in those that have reached the olfactory bulb. We show that two of the naturally occurring Notch1 activators, Jagged1 and Delta1, are also expressed in the SVZ and within the RMS in the adult mouse brain. Finally, using a model of cortical stab wound, we show that the astrogliogenic response of the SVZ to injury is accompanied by activation of the Notch pathway.

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  1. Alvarez-Buylla A, Lim DA: For the long run: maintaining germinal niches in the adult brain. Neuron 2004;41:683–686.
  2. Lois C, Alvarez-Buylla A: Long-distance neuronal migration in the adult mammalian brain. Science 1994;264:1145–1148.
  3. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeder EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R: A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature 1999;398:518–521.
  4. Struhl G, Greenwald I: Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 1999;398:522–524.
  5. Fortini ME, Artavanis-Tsakonas S: The suppressor of hairless protein participates in notch receptor signaling. Cell 1994;79:273–282.
  6. Jarriault S, Brou C, Logeat F, Schroeter E, Kapan R, Israel A: Signaling downstream of activated mammalian Notch. Nature 1995;377:355–358.
  7. Kato H, Taniguchi Y, Kurooka H, Minoguchi S, Sakai T, Nomura-Okazaki S, Tamura K, Honjo T: Involvement of RBP-J in biological functions of mouse Notch1 and its derivatives. Development 1997;124:4133–4141.
  8. Artavanis TS, Matsuno K, Fortini ME: Notch signaling. Science 1995;268:225–232.
  9. Mason H, Rakowiecki S, Gridley T, Fishell G: Notch activity promotes cell survival in the developing central nervous system. Dev Neurosci 2006;28:49–57.

    External Resources

  10. Sestan N, Artavanis-Tsakonas S, Rakic P: Contact-dependent inhibition of cortical neurite growth mediated by notch signaling. Science 1999;286:741–746.
  11. Franklin JL, Berechid BE, Cutting FB, Presente A, Chambers CB, Foltz DR, Ferreira A, Nye JS: Autonomous and non-autonomous regulation of mammalian neurite development by Notch1 and Delta1. Curr Biol 1999;9:1448–1457.
  12. Crowner D, Le Gall M, Gates MA, Giniger E: Notch steers Drosophila ISNb motor axons by regulating the Abl signaling pathway. Curr Biol 2003;13:967–972.
  13. Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T: Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. Neuron 2001;29:45–55.
  14. Hitoshi S, Alexson T, Tropepe V, Donoviel D, Elia AJ, Nye JS, Conlon RA, Mak TW, Bernstein A, van der Kooy D: Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev 2002;16:846–858.
  15. Ge W, Martinowich K, Wu X, He F, Miyamoto A, Fan G, Weinmaster G, Sun YE: Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene activation. J Neurosci Res 2002;69:848–860.
  16. Bernardos RL, Lentz SI, Wolfe MS, Raymond PA: Notch-Delta signaling is required for spatial patterning and Muller glia differentiation in the zebrafish retina. Dev Biol 2005;278:381–395.
  17. Morrison SJ, Perez SE, Qiao Z, Verdi JM, Hicks C, Weinmaster G, Anderson DJ: Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell 2000;101:499–510.
  18. Gaiano N, Nye JS, Fishell G: Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 2000;26:395–404.
  19. Wang S, Sdrulla AD, diSibio G, Bush G, Nofziger D, Hicks C, Weinmaster G, Barres B: Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 1998;21:63–75.
  20. Givogri MI, Costa RM, Schonmann V, Silva AJ, Campagnoni AT, Bongarzone ER: Central nervous system myelination in mice with deficient expression of Notch1 receptor. J Neurosci Res 2002;67:309–320.
  21. Cui XY, Hu QD, Tekaya M, Shimoda Y, Ang BT, Nie DY, Sun L, Hu WP, Karsak M, Duka T, Takeda Y, Ou LY, Dawe GS, Yu FG, Ahmed S, Jin LH, Schachner M, Watanabe K, Arsenijevic Y, Xiao ZC: NB-3/Notch1 pathway via Deltex1 promotes neural progenitor cell differentiation into oligodendrocytes. J Biol Chem 2004;279:25858–25865.
  22. Higuchi M, Kiyama H, Hayakawa T, Hamada Y, Tsujimoto Y: Differential expression of Notch1 and Notch2 in developing and adult mouse brain. Brain Res Mol Brain Res 1995;29:263–272.
  23. Givogri MI, Ghiani C, de Vellis J, Bongarzone ER: Notch 1 is expressed in cells emerging from the subventricular zone of the mouse brain. Soc Neurosci 31st Annu Meet, San Diego, 2001.
  24. Irvin DK, Zurcher SD, Nguyen T, Weinmaster G, Kornblum HI: Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development. J Comp Neurol 2001;436:167–181.
  25. Stump G, Durrer A, Klein AL, Lutolf S, Suter U, Taylor V: Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain. Mech Dev 2002;114:153–159.
  26. Gritti A, Bonfanti L, Doetsch F, Caille I, Alvarez-Buylla A, Lim DA, Galli R, Verdugo JM, Herrera DG, Vescovi AL: Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents. J Neurosci 2002;22:437–445.
  27. Gritti A, Frolichsthal-Schoeller P, Galli R, Parati EA, Cova L, Pagano SF, Bjornson CR, Vescovi AL: Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain. J Neurosci 1999;19:3287–3297.
  28. Givogri MI, Schonmann V, Cole R, De Vellis J, Bongarzone ER: Notch1 and Numb genes are inversely expressed as oligodendrocytes differentiate. Dev Neurosci 2003;25:50–64.
  29. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A: Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 1997;17:5046–5061.
  30. Gotts JE, Chesselet MF: Migration and fate of newly born cells after focal cortical ischemia in adult rats. J Neurosci Res 2005;80:160–171.
  31. Goings GE, Sahni V, Szele FG: Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury. Brain Res 2004;996:213–226.
  32. Tramontin AD, Garcia-Verdugo JM, Lim DA, Alvarez-Buylla A: Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment. Cereb Cortex 2003;13:580–587.
  33. Alexson T, Hitoshi S, Coles B, Bernstein A, van der Kooy D: Notch signaling is required to maintain all neural stem cell populations – Irrespective of spatial or temporal niche. Dev Neurosci 2006;28:34–48.

    External Resources

  34. Lindsell CE, Boulter J, diSibio G, Gossler A, Weinmaster G: Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development. Mol Cell Neurosci 1996;8:14–27.
  35. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisén U: Identification of a neural stem cell in the adult mammalian central nervous system 1999;96:25–34.
  36. Chambers CB, Peng Y, Nguyen H, Gaiano N, Fishell G, Nye JS: Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors. Development 2001;128:689–702.
  37. Kuhn HG, Dickinson-Anson H, Gage FH: Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 1996;16:2027–2033.
  38. Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH: Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 2003;130:391–399.
  39. Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E: Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci USA 1999;96:5263–5267.
  40. Cameron HA, McKay RD: Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 2001;435:406–417.
  41. Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C, Logvinova A, Greenberg DA: Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2003;2:175–183.
  42. Fawcett JW, Asher RA: The glial scar and central nervous system repair. Brain Res Bull 1999;49:377–391.
  43. Muir EM, Adcock KH, Morgenstern DA, Clayton R, von Stillfried N, Rhodes K, Ellis C, Fawcett JW, Rogers JH: Matrix metalloproteases and their inhibitors are produced by overlapping populations of activated astrocytes. Brain Res Mol Brain Res 2002;100:103–117.
  44. Okada S, Nakamura M, Mikami Y, Shimazaki T, Mihara M, Ohsugi Y, Iwamoto Y, Yoshizaki K, Kishimoto T, Toyama Y, Okano H: Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury. J Neurosci Res 2004;76:265–276.
  45. Sandvig A, Berry M, Barrett LB, Butt A, Logan A: Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: expression, receptor signaling, and correlation with axon regeneration. Glia 2004;46:225–251.
  46. John GR, Shankar SL, Zagardo B, Massimi A, Lee S, Raine CS, Brosnan CF: Mutiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med 2002;8:1115–1121.

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