Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Apr 1;110(4):1275–1283. doi: 10.1083/jcb.110.4.1275

Deposition and role of thrombospondin in the histogenesis of the cerebellar cortex

PMCID: PMC2116075  PMID: 2182649

Abstract

The patterns of deposition of thrombospondin (TSP), a trimeric extracellular matrix glycoprotein, were determined during the initial establishment of the external granule cell layer and the subsequent inward migration of granule cells forming the molecular and (internal) granule cell layers. The early homogeneous deposition of TSP became restricted to the rhombic lip in the region of granule cell exit from the neuroepithelium, and was present between migrating granule cells. During the later inward migration of granule cells, little TSP was associated with dividing granule cells; it was enriched in premigratory granule cells. With the cessation of migration, TSP was lost except in association with fasciculating axons in the molecular layer where staining persisted briefly. At the EM level, TSP was associated with the leading process of granule cells as they associated with Bergmann glial cells and migrated through the molecular layer. TSP was present within granule cell axons; Purkinje cells and their dendrites, as well as Bergmann glial fibers and endfeet were negative for TSP. When anti- TSP antibodies were added to explant cultures of cerebellar cortex during active granule cell migration, a dose-dependent inhibition of migration was observed. In control cultures, granule cells migrated into the (internal) granule cell layer, while granule cells exposed to anti-TSP antibodies were arrested within the external granule cell layer. These results suggest that TSP plays an important role in the histogenesis of the cerebellar cortex by influencing granule cell migration.

Full Text

The Full Text of this article is available as a PDF (3.1 MB).

Selected References

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

  1. Altman J., Bayer S. A. Prenatal development of the cerebellar system in the rat. I. Cytogenesis and histogenesis of the deep nuclei and the cortex of the cerebellum. J Comp Neurol. 1978 May 1;179(1):23–48. doi: 10.1002/cne.901790104. [DOI] [PubMed] [Google Scholar]
  2. Altman J. Postnatal development of the cerebellar cortex in the rat. I. The external germinal layer and the transitional molecular layer. J Comp Neurol. 1972 Jul;145(3):353–397. doi: 10.1002/cne.901450305. [DOI] [PubMed] [Google Scholar]
  3. Aquino D. A., Margolis R. U., Margolis R. K. Immunocytochemical localization of a chondroitin sulfate proteoglycan in nervous tissue. II. Studies in developing brain. J Cell Biol. 1984 Sep;99(3):1130–1139. doi: 10.1083/jcb.99.3.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Chun J. J., Shatz C. J. A fibronectin-like molecule is present in the developing cat cerebral cortex and is correlated with subplate neurons. J Cell Biol. 1988 Mar;106(3):857–872. doi: 10.1083/jcb.106.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chuong C. M., Crossin K. L., Edelman G. M. Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers. J Cell Biol. 1987 Feb;104(2):331–342. doi: 10.1083/jcb.104.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chuong C. M., Edelman G. M. Alterations in neural cell adhesion molecules during development of different regions of the nervous system. J Neurosci. 1984 Sep;4(9):2354–2368. doi: 10.1523/JNEUROSCI.04-09-02354.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Delpech A., Girard N., Delpech B. Localization of hyaluronectin in the nervous system. Brain Res. 1982 Aug 12;245(2):251–257. doi: 10.1016/0006-8993(82)90807-1. [DOI] [PubMed] [Google Scholar]
  9. Dixit V. M., Grant G. A., Santoro S. A., Frazier W. A. Isolation and characterization of a heparin-binding domain from the amino terminus of platelet thrombospondin. J Biol Chem. 1984 Aug 25;259(16):10100–10105. [PubMed] [Google Scholar]
  10. Erickson C. A. Control of pathfinding by the avian trunk neural crest. Development. 1988;103 (Suppl):63–80. doi: 10.1242/dev.103.Supplement.63. [DOI] [PubMed] [Google Scholar]
  11. Erickson H. P., Taylor H. C. Hexabrachion proteins in embryonic chicken tissues and human tumors. J Cell Biol. 1987 Sep;105(3):1387–1394. doi: 10.1083/jcb.105.3.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grumet M., Hoffman S., Crossin K. L., Edelman G. M. Cytotactin, an extracellular matrix protein of neural and non-neural tissues that mediates glia-neuron interaction. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8075–8079. doi: 10.1073/pnas.82.23.8075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hatten M. E., Furie M. B., Rifkin D. B. Binding of developing mouse cerebellar cells to fibronectin: a possible mechanism for the formation of the external granular layer. J Neurosci. 1982 Sep;2(9):1195–1206. doi: 10.1523/JNEUROSCI.02-09-01195.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hay E. D. Extracellular matrix. J Cell Biol. 1981 Dec;91(3 Pt 2):205s–223s. doi: 10.1083/jcb.91.3.205s. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krayanek S. Structure and orientation of extracellular matrix in developing chick optic tectum. Anat Rec. 1980 May;197(1):95–109. doi: 10.1002/ar.1091970109. [DOI] [PubMed] [Google Scholar]
  16. Krystosek A., Seeds N. W. Plasminogen activator secretion by granule neurons in cultures of developing cerebellum. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7810–7814. doi: 10.1073/pnas.78.12.7810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lahav J., Lawler J., Gimbrone M. A. Thrombospondin interactions with fibronectin and fibrinogen. Mutual inhibition in binding. Eur J Biochem. 1984 Nov 15;145(1):151–156. doi: 10.1111/j.1432-1033.1984.tb08534.x. [DOI] [PubMed] [Google Scholar]
  18. Lahav J., Schwartz M. A., Hynes R. O. Analysis of platelet adhesion with a radioactive chemical crosslinking reagent: interaction of thrombospondin with fibronectin and collagen. Cell. 1982 Nov;31(1):253–262. doi: 10.1016/0092-8674(82)90425-1. [DOI] [PubMed] [Google Scholar]
  19. Lawler J., Derick L. H., Connolly J. E., Chen J. H., Chao F. C. The structure of human platelet thrombospondin. J Biol Chem. 1985 Mar 25;260(6):3762–3772. [PubMed] [Google Scholar]
  20. Lawler J., Weinstein R., Hynes R. O. Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors. J Cell Biol. 1988 Dec;107(6 Pt 1):2351–2361. doi: 10.1083/jcb.107.6.2351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Letourneau P. C., Madsen A. M., Palm S. L., Furcht L. T. Immunoreactivity for laminin in the developing ventral longitudinal pathway of the brain. Dev Biol. 1988 Jan;125(1):135–144. doi: 10.1016/0012-1606(88)90066-8. [DOI] [PubMed] [Google Scholar]
  22. Lindner J., Rathjen F. G., Schachner M. L1 mono- and polyclonal antibodies modify cell migration in early postnatal mouse cerebellum. 1983 Sep 29-Oct 5Nature. 305(5933):427–430. doi: 10.1038/305427a0. [DOI] [PubMed] [Google Scholar]
  23. MIALE I. L., SIDMAN R. L. An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp Neurol. 1961 Oct;4:277–296. doi: 10.1016/0014-4886(61)90055-3. [DOI] [PubMed] [Google Scholar]
  24. Majack R. A., Cook S. C., Bornstein P. Control of smooth muscle cell growth by components of the extracellular matrix: autocrine role for thrombospondin. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9050–9054. doi: 10.1073/pnas.83.23.9050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Margolis R. U., Margolis R. K., Chang L. B., Preti C. Glycosaminoglycans of brain during development. Biochemistry. 1975 Jan 14;14(1):85–88. doi: 10.1021/bi00672a014. [DOI] [PubMed] [Google Scholar]
  26. McLoon S. C., McLoon L. K., Palm S. L., Furcht L. T. Transient expression of laminin in the optic nerve of the developing rat. J Neurosci. 1988 Jun;8(6):1981–1990. doi: 10.1523/JNEUROSCI.08-06-01981.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Menoud P. A., Debrot S., Schowing J. Mouse neural crest cells secrete both urokinase-type and tissue-type plasminogen activators in vitro. Development. 1989 Aug;106(4):685–690. doi: 10.1242/dev.106.4.685. [DOI] [PubMed] [Google Scholar]
  28. Moonen G., Grau-Wagemans M. P., Selak I. Plasminogen activator-plasmin system and neuronal migration. Nature. 1982 Aug 19;298(5876):753–755. doi: 10.1038/298753a0. [DOI] [PubMed] [Google Scholar]
  29. Mumby S. M., Raugi G. J., Bornstein P. Interactions of thrombospondin with extracellular matrix proteins: selective binding to type V collagen. J Cell Biol. 1984 Feb;98(2):646–652. doi: 10.1083/jcb.98.2.646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Murphy-Ullrich J. E., Hök M. Thrombospondin modulates focal adhesions in endothelial cells. J Cell Biol. 1989 Sep;109(3):1309–1319. doi: 10.1083/jcb.109.3.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. O'Shea K. S., Dixit V. M. Unique distribution of the extracellular matrix component thrombospondin in the developing mouse embryo. J Cell Biol. 1988 Dec;107(6 Pt 2):2737–2748. doi: 10.1083/jcb.107.6.2737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rakic P. Neuron-glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electronmicroscopic study in Macacus Rhesus. J Comp Neurol. 1971 Mar;141(3):283–312. doi: 10.1002/cne.901410303. [DOI] [PubMed] [Google Scholar]
  33. Ripellino J. A., Bailo M., Margolis R. U., Margolis R. K. Light and electron microscopic studies on the localization of hyaluronic acid in developing rat cerebellum. J Cell Biol. 1988 Mar;106(3):845–855. doi: 10.1083/jcb.106.3.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ripellino J. A., Margolis R. U., Margolis R. K. Immunoelectron microscopic localization of hyaluronic acid-binding region and link protein epitopes in brain. J Cell Biol. 1989 May;108(5):1899–1907. doi: 10.1083/jcb.108.5.1899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sanes J. R. Extracellular matrix molecules that influence neural development. Annu Rev Neurosci. 1989;12:491–516. doi: 10.1146/annurev.ne.12.030189.002423. [DOI] [PubMed] [Google Scholar]
  36. Silverstein R. L., Harpel P. C., Nachman R. L. Tissue plasminogen activator and urokinase enhance the binding of plasminogen to thrombospondin. J Biol Chem. 1986 Jul 25;261(21):9959–9965. [PubMed] [Google Scholar]
  37. Silverstein R. L., Leung L. L., Harpel P. C., Nachman R. L. Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator. J Clin Invest. 1984 Nov;74(5):1625–1633. doi: 10.1172/JCI111578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Silverstein R. L., Nachman R. L., Leung L. L., Harpel P. C. Activation of immobilized plasminogen by tissue activator. Multimolecular complex formation. J Biol Chem. 1985 Aug 25;260(18):10346–10352. [PubMed] [Google Scholar]
  39. Stewart G. R., Pearlman A. L. Fibronectin-like immunoreactivity in the developing cerebral cortex. J Neurosci. 1987 Oct;7(10):3325–3333. doi: 10.1523/JNEUROSCI.07-10-03325.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Taraboletti G., Roberts D. D., Liotta L. A. Thrombospondin-induced tumor cell migration: haptotaxis and chemotaxis are mediated by different molecular domains. J Cell Biol. 1987 Nov;105(5):2409–2415. doi: 10.1083/jcb.105.5.2409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Valinsky J. E., Le Douarin N. M. Production of plasminogen activator by migrating cephalic neural crest cells. EMBO J. 1985 Jun;4(6):1403–1406. doi: 10.1002/j.1460-2075.1985.tb03793.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Varani J., Dixit V. M., Fligiel S. E., McKeever P. E., Carey T. E. Thrombospondin-induced attachment and spreading of human squamous carcinoma cells. Exp Cell Res. 1986 Dec;167(2):376–390. doi: 10.1016/0014-4827(86)90178-3. [DOI] [PubMed] [Google Scholar]
  43. Verrall S., Seeds N. W. Characterization of 125I-tissue plasminogen activator binding to cerebellar granule neurons. J Cell Biol. 1989 Jul;109(1):265–271. doi: 10.1083/jcb.109.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Verrall S., Seeds N. W. Tissue plasminogen activator binding to mouse cerebellar granule neurons. J Neurosci Res. 1988 Oct-Dec;21(2-4):420–425. doi: 10.1002/jnr.490210233. [DOI] [PubMed] [Google Scholar]
  45. Vischer P., Völker W., Schmidt A., Sinclair N. Association of thrombospondin of endothelial cells with other matrix proteins and cell attachment sites and migration tracks. Eur J Cell Biol. 1988 Oct;47(1):36–46. [PubMed] [Google Scholar]

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

RESOURCES