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Developmental Changes in Progenitor Cell Responsiveness to Bone Morphogenetic Proteins Differentially Modulate Progressive CNS Lineage Fate

Mehler M.F. · Mabie P.C. · Zhu G. · Gokhan S. · Kessler J.A.

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Departments of Neurology and Neuroscience and the Rose F. Kennedy Center for Research in Mental Retardation and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, N.Y., USA

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Dev Neurosci 2000;22:74–85

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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: February 15, 2000
Issue release date: February 2000

Number of Print Pages: 12
Number of Figures: 6
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE

Abstract

Although multipotent progenitor cells capable of generating neurons, astrocytes and oligodendrocytes are present within the germinal zones of the brain throughout embryonic, postnatal and adult life, the different neural cell types are generated within discrete temporospatial developmental windows. This might suggest that multipotent progenitor cells encounter different signals during each developmental stage, thus accounting for separate waves of lineage commitment and cellular differentiation. This study demonstrates, however, that progenitor cell responses to the same class of signals, the bone morphogenetic proteins (BMPs), change during ontogeny, and that these same signals may thus initiate progenitor cell elaboration of several different lineages. BMPs promote cell death and inhibit the proliferation of early (embryonic day 13, E13) ventricular zone progenitor cells. At later embryonic (E16) stages of cerebral cortical development, BMPs exhibit a concentration-dependent dissociation of cellular actions, with either enhancement of neuronal and astroglial elaboration (at 1–10 ng/ml) or potentiation of cell death (at 100 ng/ml). Finally, during the period of perinatal cortical gliogenesis, BMPs enhance astroglial lineage elaboration. By contrast, oligodendroglial lineage elaboration is inhibited by the BMPs at all stages. Further, application of the BMP antagonist noggin to cultured progenitors promotes the generation of oligodendrocytes, indicating that endogenous BMP signaling can actively suppress oligodendrogliogenesis. These observations suggest that developmental changes in neural progenitor cell responsiveness to the BMPs may represent a novel mechanism for orchestrating context-specific cellular events such as lineage elaboration and cellular viability.

© 2000 S. Karger AG, Basel


References

  1. McKay R (1997): Stem cells in the central nervous system. Science 276:66–71.
  2. Weiss S, Reynolds BA, Vescovi AL, Morshead C, Craig CG, van der Kooy D (1996): Is there a neural stem cell in the mammalian forebrain? Trends Neurosci 19:387–393.
  3. Edlund T, Jessell TM (1999): Progression from extrinsic to intrinsic signaling in cell fate specification: A view from the nervous system. Cell 96:211–224.
  4. Morrison SJ, Shah NW, Anderson DJ (1997): Regulatory mechanisms in stem cell biology. Cell 88:287–298.
  5. Qian X, Davis AD, Goderie SK, Temple S (1997): FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells. Neuron 18:81–93.
  6. Burrows RC, Wancio D, Levitt P, Lillien L (1997): Response diversity and the timing of progenitor cell maturation are regulated by developmental changes in EGFR expression in the cortex. Neuron 19:251–267.
  7. Kilpatrick TF, 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 15:3653–3661.
  8. Vescovi AL, Reynolds BA, Fraser DD, Weiss S (1993): bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells. Neuron 11:951–966.
  9. Threadgil DW, Flugosz AA, Hansen AA, Tennenbaum T, Lichti U, Yee D, LaMantia C, Mourton T, Herrup K, Harris, RC (1995): Targeted disruption of mouse EGF receptor: Effect of genetic background on mutant phenotype. Science 269:230–234.
  10. 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 208:166–188.
  11. Massagué J (1998): TGF-β signal transduction. Annu Rev Biochem 67:753–791.
  12. Hogan BL (1996): Bone morphogenetic proteins: Multifunctional regulators of vertebrate development. Genes Dev 10:1580–1594.
  13. Mehler MF, Kessler JA (1997): Bone morphogenetic proteins in the nervous system. Trends Neurosci 20:309–317.
  14. Kretzschmar M, Doody J, Massagu J (1997): Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smad1. Nature 389:618–622.
  15. Neubüser A, Peters H, Bailing R, Martin GR (1997): Antagonistic interactions between FGF and BMP signaling pathways: A mechanism for positioning the sites of tooth formation. Cell 90:247–255.
  16. Nakashima K, Yangisawa M, Arakawa H, Kimura N, Tatsuhiro H, Kawabata M, Miyazono K, Taga T (1999): Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science 284:479–482.
  17. Mabie PC, Mehler MF, Papavasiliou A, Song Q, Kessler JA (1997): Bone morphogenetic proteins induce astroglial differentiation of oligodendroglial-astroglial progenitor cells. J Neurosci 17:4112–4120.
  18. Zhang D, Mehler MF, Song Q, Kessler JA (1998): Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression. J Neurosci 18:3314–3326.
  19. Mehler MF, Marmur R, Gross R, Mabie PC, Zang Z, Papavasiliou A, Kessler JA (1995): Cytokines regulate the cellular phenotype of developing neural lineage species. Int J Dev Neurosci 13:213–240.
  20. Soderstrom S, Bengtsson H, Ebendal T (1996): Expression of serine/threonine kinase receptors including the bone morphogenetic factor type II receptor in the developing and adult rat brain. Cell Tissue Res 286:269–279.
  21. Gross RE, Mehler MF, Mabie PC, Santschi L, Ngo P, Kessler JA (1996): Bone morphogenetic proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells. Neuron 17:595–606.
  22. Mabie PC, Mehler M, Kessler JA (1999): Multiple roles of bone morphogenetic protein signaling in the regulation of cortical cell number and phenotype. J Neurosci 19:7077–7088.
  23. Shah NM, Groves AK, Anderson DJ (1996): Alternative neural crest cell fates are instructively promoted by TGF beta superfamily members. Cell 85:331–343.
  24. Shou J, Rim PC, Calof AL (1999): BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription factor. Nat Neurosci 2:339–345.
  25. Cohen RI, Marmur R, Norton WT, Mehler MF, Kessler JA (1996): Nerve growth factor and neurotrophin-3 differentially regulate the proliferation and the survival of developing rat brain oligodendrocytes. J Neurosci 16:6433–6442.
  26. Mehler MF, Rozental R, Dougherty M, Spray DC, Kessler JA (1993): Cytokine regulation of neuronal differentiation of hippocampal progenitor cells. Nature 362:62–65.
  27. Marmur, R, Mabie PC, Gokhan S, Song Q, Kessler JA, Mehler MF (1998): Isolation and developmental characterization of cerebral cortical multipotent progenitors. Dev Biol 204:577–591.
  28. Zhu G, Mehler MF, Mabie PC, Kessler JA (1999): Developmental changes in progenitor cell responsiveness to cytokines. J Neurosci Res 56:131–145.
  29. Gard AL, Pfeiffer SE, Williams WC (1993): Immunopanning and developmental stage- specific cultures of oligodendrocyte progenitors (O4+/O1–) from the postnatal rodent cerebrum. Neuroprotocols 2:209–220.
  30. Reynolds BA, Weiss S (1992): Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710.
  31. Kerr JF, Gobe GC, Winterford CM, Harmon BV (1995): Anatomical methods in cell death; in Schwartz LM, Osborne BA (eds): Methods in Cell Biology. New York, Academic Press, pp 1–26.
  32. Goldman JE, Zerlin M, Newman S, Zhang L, Gensert J (1997): Fate determination and migration of progenitors in the postnatal mammalian CNS. Dev Neurosci 19:42–48.
  33. Lillien LE (1998): Neural progenitors and stem cells: Mechanisms of progenitor heterogeneity. Curr Opin Neurobiol 8:37–44.
  34. Edwards MA, Yamamoto M, Caviness VS (1990): Organization of radial glia and related cells in the developing murine CNS, an analysis based upon a new monoclonal antibody marker. Neuroscience 36:121–144.
  35. Song Q, Mehler MF, Kessler JA (1998): Bone morphogenetic proteins induce apoptosis and growth factor dependence of cultured sympathoadrenal progenitor cells. Dev Biol 196:119–127.
  36. Varley JE, McPherson CE, Zou H, Niswander L, Maxwell GD (1998): Expression of a constitutively active type I BMP receptor using a retroviral vector promotes the development of adrenergic cells in neural crest cultures. Dev Biol 196:107–118.
  37. Weiwei L, Cogswell CA, LoTurco LL (1998): Neuronal differentiation of precursors in the neocortical ventricular zone is triggered by BMP. J Neurosci 18:8853–8862.
  38. Furuta Y, Piston DW, Hogan BL (1997): Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development 124:2203–2212.
  39. Graham A, Francis-West P, Brickell P, Lumsden A (1994): The signalling molecule BMP4 mediates apoptosis in the rhombencephalic neural crest. Nature 372:684–686.
  40. Graham A, Koentges G, Lumsden A (1996): Neural crest apoptosis and the establishment of craniofacial pattern: An honorable death. Mol Cell Neurosci 8:76–83.
  41. Fishell G (1999): BMPs: Timer to murder and create? Nat Neurosci 2:301–302.
  42. Zhu G, Mehler MF, Kessler JA (1999): Developmental changes in progenitor cell lineage commitment do not reflect EGF receptor signaling. Soc Neurosci Abstr (in press).
  43. Rajan P, McKay RD (1998): Multiple routes to astrocytic differentiation in the CNS. J Neurosci 18:3620–3629.
  44. Ware CB, Horowitz MC, Renshow BR, Hunt JS, Liggit D, Koblar SA, Gliniak BC, McKenne HJ, Papayannopoulo T, Thoma B, Cheng L, Donovan PJ, Peschon JJ, Bartlett PF, Willis CR, Wright BD, Carpenter M (1995): Targeted disruption of the low affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in prenatal death. Development 121:1283–1299.
  45. 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 76:414–418.
  46. Mehler MF, Mabie PC, Marmur R, Kessler JA (1996): Differential regulation of radial glia and astroglial lineage elaboration from embryonic subventricular zone (SVZ) progenitor cells by leukemia inhibitory factor-β (LIFβR) receptor activation and bone morphogenetic proteins (BMPs). Soc Neurosci Abstr 22:285.
  47. Hosoya T, Takizawa K, Nitta K, Hotta Y (1995): Glial cells missing: A binary switch between neuronal and glial determination in Drosophila. Cell 82:1025–1036.
  48. Akiyama-Oda Y, Hosoya T, Hotta Y (1999): Asymmetric cell division of thoracic neuroblast 6–4 to bifurcate glial and neuronal lineage in Drosophila. Development 126:1967–1974.
  49. Miller AA, Bernardoni R, Giangrande A (1998): Positive autoregulation of the glial promoting factor glide/gcm. EMBO J 17:6316–6326.
  50. Giesen K, Hummel T, Stollewerk A, Harrison S, Travers A, Klambt C (1997): Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes. Development 124:2307–2316.
  51. Granderath S, Stollewerk A, Grieg S, Goodman CS, O’Kane CJ, Klambt C (1999): Loco encodes an RGS protein required for Drosophila glial differentiation. Development 126:1781–1791.

Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: February 15, 2000
Issue release date: February 2000

Number of Print Pages: 12
Number of Figures: 6
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE


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