Oligodendrocyte Development and Myelination in Serum-Free Aggregating Brain Cell Cultures

  • P. Honegger
Part of the NATO ASI Series book series (NSSA, volume 142)


A growing body of evidence suggests that cell-cell signalling plays a crucial role in neural development from the earliest stages of neurogenesis up to relatively late developmental events such as myelination. Cell-cell communication appears to be mediated by direct cell-cell contact as well as by specific diffusible substances. In addition to cellular signals, hormones may also greatly influence the course of brain development. To elucidate these intricate mechanisms, research is required at both the molecular and cellular level. Aggregating brain cell cultures (for reviews, see refs. 1–3) appear to offer a particularly suitable model to study these problems at the cellular level. The cultures described here are prepared from fetal brain tissue by allowing mechanically dissociated cells to reaggregate under controlled conditions into small, uniform spheres (4). The resulting three-dimensional cell structure of each sphere provides a maximum of cell-cell interactions, and enables the cells to rearrange and to develop in a histotypic fashion. Histotypic cellular organization and maturation occurs also in aggreate cultures prepared and grown in a chemically defined medium (3,5). These serum-free cultures can be obtained in large quantities, and may be used at different developmental stages for multidisciplinary studies. Since the cellular composition of aggregate cultures reflects that of the original brain tissue, the development of all constituents can be studied, and regional differences in the behavior of cells can be investigated. Serum-free aggregating cell cultures of fetal rat telencephalon have been used in a number of developmental studies. The present report reviews some of this work related to oligodendroglial development and myelin synthesis.


Thyroid Hormone Myelin Basic Protein Brain Cell Culture Aggregate Culture Oligodendrocyte Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. A. Moscona, Recombination of dissociated cells and the development of cell aggregates, in: “Cells and Tissues in Culture”, E. N. Willmer, ed., Academic Press, New York (1965).Google Scholar
  2. 2.
    N. W. Seeds, Differentiation of aggregating brain cell cultures, in: “Tissue Culture of the Nervous System”, G. Sato, ed., Plenum Press, New York (1973).Google Scholar
  3. 3.
    P. Honegger, Biochemical differentiation in serum-free aggregating brain cell cultures, in: “Cell Culture in the Neurosciences”, J. E. Bottenstein and G. Sato, eds., Plenum Publishing Corp., New York (1985).Google Scholar
  4. 4.
    P. Honegger and E. Richelson, Biochemical differentiation of mechanically dissociated mammalian brain in aggregating cell culture, Brain Res., 109: 335 (1976).CrossRefGoogle Scholar
  5. 5.
    P. Honegger, D. Lenoir, and P. Favrod, Growth and differentiation of aggregating fetal brain cells in a serum-free defined medium, Nature, 282: 305 (1979).CrossRefGoogle Scholar
  6. 6.
    D. Lenoir and P. Honegger, Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures, Dev. Brain. Res., 7: 205 (1983).CrossRefGoogle Scholar
  7. 7.
    G. Almazan, P. Honegger, and J.-M. Matthieu, Triiodothyronine stimulation of oligodendroglial differentiation and myelination. A developmental study, Dev. Neurosci., 7: 45 (1985).CrossRefGoogle Scholar
  8. 8.
    B. Guentert-Lauber and P. Honegger, Responsiveness of astrocytes in serum-free aggregate cultures to epidermal growth factor: dependence on the cell cycle and the epidermal growth factor concentration, Dev. Neurosci., 7: 286 (1985).CrossRefGoogle Scholar
  9. 9.
    B. Morell and E. R. Froesch, Fibroblasts as an experimental tool in metabolic and hormone studies — effect of insulin and nonsuppressible insulin-like activity (NSILA-S) on fibroblasts in culture, Europ. J. Clin. Invest., 3: 119 (1973).CrossRefGoogle Scholar
  10. 10.
    A. J. D’Ercole, G. T. Appelwhite, and L. E. Underwood, Evidence that somatomedin is synthesized by multiple tissues in the fetus, Dev. Biol., 75: 315 (1980).CrossRefGoogle Scholar
  11. 11.
    M. Binoux, P. Honsenlopp, C. Lasarre, and N. Hardouin, Production of insulin-like growth factor and their carriers by rat pituitary gland and brain expiants in culture, FEBS Lett., 124: 178 (1981).CrossRefGoogle Scholar
  12. 12.
    G. K. Haselbacher, M. E. Schwab, A. Pasi, and R. E. Humbel, Symposium Insulin-like Growth Factors/Somatomedins, Nairobi, Kenya, 13–15 November, p. 75 (abstract) 1982.Google Scholar
  13. 13.
    F. A. McMorris, T. M. Smith, S. DeSalvo, and R. W. Furlanetto, Insulin-like growth factor I/Somatomedin C: a potent inducer of oligodendrocyte development, Proc. Natl. Acad. Sci., USA 83: 822 (1986).CrossRefGoogle Scholar
  14. 14.
    P. Honegger and B. Guentert-Lauber, Epidermal growth factor (EGF) stimulation of cultured brain cells. I. Enhancement of the developmental increase in glial enzymatic activity, Dev. Brain. Res., 11: 245 (1983).CrossRefGoogle Scholar
  15. 15.
    G. Almazan, P. Honegger, J.-M. Matthieu, and B. Guentert-Lauber, Epidermal growth factor and bovine growth hormone stimulate differentiation and myelination of brain cell aggregates in culture, Dev. Brain Res., 21: 257 (1985).CrossRefGoogle Scholar
  16. 16.
    B. Guentert-Lauber and P. Honegger, Epidermal growth factor (EGF) stimulation of cultured brain cells. II. Increased production of extracellular soluble proteins, Dev. Brain Res., 11: 253 (1983).CrossRefGoogle Scholar
  17. 17.
    C. Labarca and K. Paigen, A simple, rapid, and sensitive DNA assay procedure, Analyt. Biochem., 102: 344 (1980).CrossRefGoogle Scholar
  18. 18.
    T. Kurihara and Y. Tsukada, The regional and subcellular distribution of 2′,3′-cyclic nucleotide 3′-phosphohydrolase in the central nervous system, J. Neurochem., 14: 1167 (1967).CrossRefGoogle Scholar
  19. 19.
    M. R. Pishak and A. T. Phillips, A modified radioisotopic assay for measuring glutamine synthetase activity in tissue extract, Analyt. Biochem., 94: 82 (1979).CrossRefGoogle Scholar
  20. 20.
    A. J. Patel, A. Hunt, R. D. Gordon, and R. Balazs, The activities in different neural cell types of certain enzymes associated with the metabolic compartmentation glutamate, Dev. Brain Res., 4: 3 (1982).CrossRefGoogle Scholar
  21. 21.
    S. H. Wilson, B. K. Shrier, J. L. Farber, E. J. Thompson, R. N. Rosenberg, A. J. Blume, and M. W. Nirenberg, Markers for gene expression in cultured cells from the nervous system, J. Biol. Chem., 247: 3159 (1972).Google Scholar
  22. 22.
    P. Honegger and D. Lenoir, Triiodothyronine enhancement of neuronal differentiation in aggregating fetal rat brain cells cultured in a chemically defined medium, Brain Res., 199: 425 (1980).CrossRefGoogle Scholar
  23. 23.
    G. L. Schmidt, Development of biochemical activities associated with myelination in chick brain aggregate cultures, Brain Res., 87: 110 (1975).CrossRefGoogle Scholar
  24. 24.
    J.-M. Matthieu, P. Honegger, B. D. Trapp, S. R. Cohen, and H. de F. Webster, Myelination in rat brain aggregating cell cultures, Neuroscience, 3: 565 (1978).CrossRefGoogle Scholar
  25. 25.
    N. W. Seeds and S. C. Haffke, Cell junction and ultrastructural development of reaggregated mouse brain cell cultures, Dev. Neurosci., 1: 69 (1978).CrossRefGoogle Scholar
  26. 26.
    J. R. Sheppard, D. Brus, and J. M. Wehner, Brain reaggregate cultures: biochemical evidence for myelin membrane synthesis, J. Neurobiol., 9: 309 (1978).CrossRefGoogle Scholar
  27. 27.
    J.-M. Matthieu, P. Honegger, P. Favrod, E. Gautier, and M. Dolivo, Biochemical characterization of a myelin fraction isolated from rat brain aggregating cell cultures, J. Neurochem., 32: 869 (1979).CrossRefGoogle Scholar
  28. 28.
    E. J. Lu, W. J. Brown, R. Cole, and J. de Vellis, Ultrastructural differentiation and synaptogenesis in aggregating rotation cultures of rat cerebral cells, J. Neurosci. Res., 5: 447 (1980).CrossRefGoogle Scholar
  29. 29.
    J.-M. Matthieu, P. Honegger, P. Favrod, J. F. Poduslo, E. Costantino-Ceccarini, and R. Kristic, Myelination and demyelination in aggregating cultures of rat brain cells, in: “Tissue Culture in Neurobiology”, E. Giacobini, A. Vernadakis and A. Shahar, eds., Raven Press, New York (1980).Google Scholar
  30. 30.
    P. Honegger and J.-M. Matthieu, Myelination of aggregating fetal rat brain cell cultures grown in a chemically defined medium, in: “Neurological Mutations Affecting Myelination”, N. Baumann, ed., Elsevier/North-Holland, Amsterdam (1980).Google Scholar
  31. 31.
    R. Balazs, B. W. L. Brooksbank, A. J. Patel, A, L. Johnson, and D. A. Wilson, Incorporation of [35s]-sulfate into brain constituents during development and the effects of thyroid hormone on myelination, Brain Res., 30: 273 (1971).CrossRefGoogle Scholar
  32. 32.
    J.-M. Matthieu, P. J. Reier, and J. A. Sawchak, Proteins of rat brain myelin in neonatal hypothyroidism, Brain Res., 84: 443 (1975).CrossRefGoogle Scholar
  33. 33.
    P. J. Reier, J.-M. Matthieu, and A. W. Zimmermann, Myelin deficiency in hereditary pituitary dwarfism: a biochemical and morphological study, J. Neuropath. Exp. Neurol., 34: 465 (1975).CrossRefGoogle Scholar
  34. 34.
    J. Legrand, Effect of thyroid hormone on brain development, with particular emphasis on glial cells and myelination, Dev. Neurosci., 9: 279 (1980).Google Scholar
  35. 35.
    S. N. Walters and P. Morell, Effects of altered thyroid states on myelinogenesis, J. Neurochem., 36: 1972 (1981).CrossRefGoogle Scholar
  36. 36.
    T. Noguchi, T. Sugisaki, and Y. Tsukuda, Postnatal action of growth and thyroid hormones on the retarded cerebral myelinogenesis of Snell dwarf mice (dw), J. Neurochem., 38: 257 (1982).CrossRefGoogle Scholar
  37. 37.
    L. L. Sarliève, R. Bouchon, C. Koehl, and N. M. Neskovic, Crebroside and sulfatide biosynthesis in the brain of Snell dwarf mouse: effects of thyroxine and growth hormone in the early postnatal period, J. Neurochem., 40: 1058 (1983).CrossRefGoogle Scholar
  38. 38.
    M. Hamburgh and R. P. Bunge, Evidence for a direct effect of thyroid hormone on maturation of nervous tissue grown in vitro, Life Sci., 3: 1423 (1964).CrossRefGoogle Scholar
  39. 39.
    N. R. Bhat, L. L. Sarliève, G. Subba Rao, and R. A. Pieringer, Investigations on myelination in vitro. Regulation by thyroid hormone in cultures of dissociated brain cells from embryonic mice, J. Biol. Chem., 254: 9342 (1979).Google Scholar
  40. 40.
    N. R. Bhat, G. Shanker, and R. A. Pieringer, Investigation on myelination in vitro: regulation of 2′,3′-cyclic nucleotide 3′-phospho-hydrolase by thyroid hormone in cultures of dissociated brain cells from embryonic mice, J. Neurochem., 37: 695 (1981).CrossRefGoogle Scholar
  41. 41.
    N. R. Bhat, G. Subba Rao, and R. A. Pieringer, Investigations on myelination in vitro. Regulation of sulfolipid synthesis by thyroid hormone in cultures of dissociated brain cells from embryonic mice, J. Biol. Chem., 256: 1167 (1981).Google Scholar
  42. 42.
    G. Shanker and R. A. Pieringer, Effect of thyroid hormone on the synthesis of sialosylgalactosyl ceramide (GM4) in myelinogenic cultures of cells dissociated from embryonic mouse brain, Dev. Brain Res., 6: 169 (1983).CrossRefGoogle Scholar
  43. 43.
    G. Shanker, G. S. Rao, and R. A. Pieringer, Investigation on myelinogenesis in vitro: regulation of 5′-nucleotide activity by thyroid hormone in cultures of dissociated cells from embryonic mouse brain, J. Neurosci. Res., 11: 263 (1984).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • P. Honegger
    • 1
  1. 1.Institute of PhysiologyUniversity of LausanneLausanneSwitzerland

Personalised recommendations