Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Aug 1;111(2):635–644. doi: 10.1083/jcb.111.2.635

Extracellular matrix-associated molecules collaborate with ciliary neurotrophic factor to induce type-2 astrocyte development

PMCID: PMC2116219  PMID: 2199462

Abstract

O-2A progenitor cells give rise to both oligodendrocytes and type-2 astrocytes in vitro. Whereas oligodendrocyte differentiation occurs constitutively, type-2 astrocyte differentiation requires extracellular signals, one of which is thought to be ciliary neurotrophic factor (CNTF). CNTF, however, is insufficient by itself to induce the development of stable type-2 astrocytes. In this report we show the following: (a) that molecules associated with the extracellular matrix (ECM) cooperate with CNTF to induce stable type-2 astrocyte differentiation in serum-free cultures. The combination of CNTF and the ECM-associated molecules thus mimics the effect of FCS, which has been shown previously to induce stable type-2 astrocyte differentiation in vitro. (b) Both the ECM-associated molecules and CNTF act directly on O- 2A progenitor cells and can induce them to differentiate prematurely into type-2 astrocytes. (c) ECM-associated molecules also inhibit oligodendrocyte differentiation, even in the absence of CNTF, but this inhibition is not sufficient on its own to induce type-2 astrocyte differentiation. (d) Whereas the effect of ECM on oligodendrocyte differentiation is mimicked by basic fibroblast growth factor (bFGF), the effect of ECM on type-2 astrocyte differentiation is not. (e) The ECM-associated molecules that are responsible for inhibiting oligodendrocyte differentiation and for cooperating with CNTF to induce type-2 astrocyte differentiation are made by non-glial cells in vitro. (f) Molecules that have these activities and bind to ECM are present in the optic nerve at the time type-2 astrocytes are thought to be developing.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abney E. R., Bartlett P. P., Raff M. C. Astrocytes, ependymal cells, and oligodendrocytes develop on schedule in dissociated cell cultures of embryonic rat brain. Dev Biol. 1981 Apr 30;83(2):301–310. doi: 10.1016/0012-1606(81)90476-0. [DOI] [PubMed] [Google Scholar]
  2. Adams J. C., Watt F. M. Fibronectin inhibits the terminal differentiation of human keratinocytes. Nature. 1989 Jul 27;340(6231):307–309. doi: 10.1038/340307a0. [DOI] [PubMed] [Google Scholar]
  3. Baird A., Ling N. Fibroblast growth factors are present in the extracellular matrix produced by endothelial cells in vitro: implications for a role of heparinase-like enzymes in the neovascular response. Biochem Biophys Res Commun. 1987 Jan 30;142(2):428–435. doi: 10.1016/0006-291x(87)90292-0. [DOI] [PubMed] [Google Scholar]
  4. Bignami A., Eng L. F., Dahl D., Uyeda C. T. Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res. 1972 Aug 25;43(2):429–435. doi: 10.1016/0006-8993(72)90398-8. [DOI] [PubMed] [Google Scholar]
  5. Bottenstein J. E., Sato G. H. Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci U S A. 1979 Jan;76(1):514–517. doi: 10.1073/pnas.76.1.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eisenbarth G. S., Walsh F. S., Nirenberg M. Monoclonal antibody to a plasma membrane antigen of neurons. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4913–4917. doi: 10.1073/pnas.76.10.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gordon M. Y., Riley G. P., Watt S. M., Greaves M. F. Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment. 1987 Mar 26-Apr 1Nature. 326(6111):403–405. doi: 10.1038/326403a0. [DOI] [PubMed] [Google Scholar]
  8. Gospodarowicz D., Cheng J. Heparin protects basic and acidic FGF from inactivation. J Cell Physiol. 1986 Sep;128(3):475–484. doi: 10.1002/jcp.1041280317. [DOI] [PubMed] [Google Scholar]
  9. Hart I. K., Richardson W. D., Bolsover S. R., Raff M. C. PDGF and intracellular signaling in the timing of oligodendrocyte differentiation. J Cell Biol. 1989 Dec;109(6 Pt 2):3411–3417. doi: 10.1083/jcb.109.6.3411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hughes S. M., Lillien L. E., Raff M. C., Rohrer H., Sendtner M. Ciliary neurotrophic factor induces type-2 astrocyte differentiation in culture. Nature. 1988 Sep 1;335(6185):70–73. doi: 10.1038/335070a0. [DOI] [PubMed] [Google Scholar]
  11. Hughes S. M., Raff M. C. An inducer protein may control the timing of fate switching in a bipotential glial progenitor cell in rat optic nerve. Development. 1987 Sep;101(1):157–167. [PubMed] [Google Scholar]
  12. Kalcheim C., Barde Y. A., Thoenen H., Le Douarin N. M. In vivo effect of brain-derived neurotrophic factor on the survival of developing dorsal root ganglion cells. EMBO J. 1987 Oct;6(10):2871–2873. doi: 10.1002/j.1460-2075.1987.tb02589.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lillien L. E., Sendtner M., Rohrer H., Hughes S. M., Raff M. C. Type-2 astrocyte development in rat brain cultures is initiated by a CNTF-like protein produced by type-1 astrocytes. Neuron. 1988 Aug;1(6):485–494. doi: 10.1016/0896-6273(88)90179-1. [DOI] [PubMed] [Google Scholar]
  14. Lindahl U., Hök M. Glycosaminoglycans and their binding to biological macromolecules. Annu Rev Biochem. 1978;47:385–417. doi: 10.1146/annurev.bi.47.070178.002125. [DOI] [PubMed] [Google Scholar]
  15. Manthorpe M., Skaper S. D., Williams L. R., Varon S. Purification of adult rat sciatic nerve ciliary neuronotrophic factor. Brain Res. 1986 Mar 5;367(1-2):282–286. doi: 10.1016/0006-8993(86)91603-3. [DOI] [PubMed] [Google Scholar]
  16. Miller R. H., David S., Patel R., Abney E. R., Raff M. C. A quantitative immunohistochemical study of macroglial cell development in the rat optic nerve: in vivo evidence for two distinct astrocyte lineages. Dev Biol. 1985 Sep;111(1):35–41. doi: 10.1016/0012-1606(85)90432-4. [DOI] [PubMed] [Google Scholar]
  17. Nathan C., Srimal S., Farber C., Sanchez E., Kabbash L., Asch A., Gailit J., Wright S. D. Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins. J Cell Biol. 1989 Sep;109(3):1341–1349. doi: 10.1083/jcb.109.3.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Noble M., Murray K., Stroobant P., Waterfield M. D., Riddle P. Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature. 1988 Jun 9;333(6173):560–562. doi: 10.1038/333560a0. [DOI] [PubMed] [Google Scholar]
  19. Panayotou G., End P., Aumailley M., Timpl R., Engel J. Domains of laminin with growth-factor activity. Cell. 1989 Jan 13;56(1):93–101. doi: 10.1016/0092-8674(89)90987-2. [DOI] [PubMed] [Google Scholar]
  20. Raff M. C., Fields K. L., Hakomori S. I., Mirsky R., Pruss R. M., Winter J. Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture. Brain Res. 1979 Oct 5;174(2):283–308. doi: 10.1016/0006-8993(79)90851-5. [DOI] [PubMed] [Google Scholar]
  21. Raff M. C., Lillien L. E., Richardson W. D., Burne J. F., Noble M. D. Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature. 1988 Jun 9;333(6173):562–565. doi: 10.1038/333562a0. [DOI] [PubMed] [Google Scholar]
  22. Raff M. C., Miller R. H., Noble M. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature. 1983 Jun 2;303(5916):390–396. doi: 10.1038/303390a0. [DOI] [PubMed] [Google Scholar]
  23. Ranscht B., Clapshaw P. A., Price J., Noble M., Seifert W. Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2709–2713. doi: 10.1073/pnas.79.8.2709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Richardson W. D., Pringle N., Mosley M. J., Westermark B., Dubois-Dalcq M. A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell. 1988 Apr 22;53(2):309–319. doi: 10.1016/0092-8674(88)90392-3. [DOI] [PubMed] [Google Scholar]
  25. Roberts R. A., Spooncer E., Parkinson E. K., Lord B. I., Allen T. D., Dexter T. M. Metabolically inactive 3T3 cells can substitute for marrow stromal cells to promote the proliferation and development of multipotent haemopoietic stem cells. J Cell Physiol. 1987 Aug;132(2):203–214. doi: 10.1002/jcp.1041320204. [DOI] [PubMed] [Google Scholar]
  26. Rogelj S., Klagsbrun M., Atzmon R., Kurokawa M., Haimovitz A., Fuks Z., Vlodavsky I. Basic fibroblast growth factor is an extracellular matrix component required for supporting the proliferation of vascular endothelial cells and the differentiation of PC12 cells. J Cell Biol. 1989 Aug;109(2):823–831. doi: 10.1083/jcb.109.2.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saksela O., Moscatelli D., Sommer A., Rifkin D. B. Endothelial cell-derived heparan sulfate binds basic fibroblast growth factor and protects it from proteolytic degradation. J Cell Biol. 1988 Aug;107(2):743–751. doi: 10.1083/jcb.107.2.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stemple D. L., Mahanthappa N. K., Anderson D. J. Basic FGF induces neuronal differentiation, cell division, and NGF dependence in chromaffin cells: a sequence of events in sympathetic development. Neuron. 1988 Aug;1(6):517–525. doi: 10.1016/0896-6273(88)90182-1. [DOI] [PubMed] [Google Scholar]
  29. Stöckli K. A., Lottspeich F., Sendtner M., Masiakowski P., Carroll P., Götz R., Lindholm D., Thoenen H. Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature. 1989 Dec 21;342(6252):920–923. doi: 10.1038/342920a0. [DOI] [PubMed] [Google Scholar]
  30. Temple S., Raff M. C. Differentiation of a bipotential glial progenitor cell in a single cell microculture. Nature. 1985 Jan 17;313(5999):223–225. doi: 10.1038/313223a0. [DOI] [PubMed] [Google Scholar]
  31. Timpl R., Rohde H., Robey P. G., Rennard S. I., Foidart J. M., Martin G. R. Laminin--a glycoprotein from basement membranes. J Biol Chem. 1979 Oct 10;254(19):9933–9937. [PubMed] [Google Scholar]
  32. Vlodavsky I., Folkman J., Sullivan R., Fridman R., Ishai-Michaeli R., Sasse J., Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2292–2296. doi: 10.1073/pnas.84.8.2292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Williams B. P., Abney E. R., Raff M. C. Macroglial cell development in embryonic rat brain: studies using monoclonal antibodies, fluorescence activated cell sorting, and cell culture. Dev Biol. 1985 Nov;112(1):126–134. doi: 10.1016/0012-1606(85)90126-5. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES