Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1980 Mar 1;84(3):739–752. doi: 10.1083/jcb.84.3.739

Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury

PMCID: PMC2110577  PMID: 6244318

Abstract

In this paper the stimuli for and pattern of Schwann cell proliferation are defined under various experimental conditions. We used a tissue culture system in which fetal rat dorsal root ganglia, treated to eliminate contaminating fibroblasts (Wood, P., 1976, Brain Res. 115:361- -375), appear to recapitulate many aspects of the developing peripheral nervous system. We observed that: (a) proliferation of Schwann cells on neurites is initially rapid, but, as each neurite becomes fully ensheathed, division slows considerably and is confined to the periphery of the outgrowth; (b) during the period of rapid proliferation, excision of the ganglion causes a rapid decay in the number of dividing cells; (c) excision of the ganglion from more established cultures in which there was little ongoing proliferation resulted in a small increase in labeling at the site of excision for all Schwann cells and a substantial increase in labeling for myelin- related cells with a peak labeling period at 4 d; (d) direct mechanical injury during Wallerian degeneration is mitogenic for Schwann cells; (e) a variety of potential mitogens failed to stimulate Schwann cell proliferation, and (f) replated cells have a slightly higher level of proliferation and show a small and variable response to the addition of cAMP.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. ABERCROMBIE M., SANTLER J. E. An analysis of growth in nuclear population during Wallerian degeneration. J Cell Physiol. 1957 Dec;50(3):429–450. doi: 10.1002/jcp.1030500308. [DOI] [PubMed] [Google Scholar]
  2. Abercrombie M., Johnson M. L. Quantitative histology of Wallerian degeneration: I. Nuclear population in rabbit sciatic nerve. J Anat. 1946 Jan;80(Pt 1):37–50. [PMC free article] [PubMed] [Google Scholar]
  3. Aguayo A. J., Bray G. M., Perkins S. C. Axon-Schwann cell relationships in neuropathies of mutant mice. Ann N Y Acad Sci. 1979;317:512–531. [PubMed] [Google Scholar]
  4. Aguayo A. J., Charron L., Bray G. M. Potential of Schwann cells from unmyelinated nerves to produce myelin: a quantitative ultrastructural and radiographic study. J Neurocytol. 1976 Oct;5(8):565–573. doi: 10.1007/BF01175570. [DOI] [PubMed] [Google Scholar]
  5. Aguayo A. J., Epps J., Charron L., Bray G. M. Multipotentiality of Schwann cells in cross-anastomosed and grafted myelinated and unmyelinated nerves: quantitative microscopy and radioautography. Brain Res. 1976 Mar 5;104(1):1–20. doi: 10.1016/0006-8993(76)90643-0. [DOI] [PubMed] [Google Scholar]
  6. Aguayo A. J., Martin J. B., Bray G. M. Effects of nerve growth factor antiserum on peripheral unmyelinated nerve fibers. Acta Neuropathol. 1972;20(4):288–298. doi: 10.1007/BF00691747. [DOI] [PubMed] [Google Scholar]
  7. Asbury A. K. Schwann cell proliferation in developing mouse sciatic nerve. A radioautographic study. J Cell Biol. 1967 Sep;34(3):735–743. doi: 10.1083/jcb.34.3.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Billings-Gagliardi S., Webster H. F., O'Connell M. F. In vivo and electron microscopic observations on Schwann cells in developing tadpole nerve fibers. Am J Anat. 1974 Nov;141(3):375–391. doi: 10.1002/aja.1001410308. [DOI] [PubMed] [Google Scholar]
  9. Boynton A. L., Whitfield J. F. The different actions of normal and supranormal calcium concentrations on the proliferation of BALB/c 3T3 mouse cells. In Vitro. 1976 Jul;12(7):479–484. doi: 10.1007/BF02796490. [DOI] [PubMed] [Google Scholar]
  10. Bradley W. G., Asbury A. K. Duration of synthesis phase in neuilemma cells in mouse sciatic nerve during degeneration. Exp Neurol. 1970 Feb;26(2):275–282. doi: 10.1016/0014-4886(70)90125-1. [DOI] [PubMed] [Google Scholar]
  11. Bray D. Surface movements during the growth of single explanted neurons. Proc Natl Acad Sci U S A. 1970 Apr;65(4):905–910. doi: 10.1073/pnas.65.4.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Brockes J. P., Fields K. L., Raff M. C. A surface antigenic marker for rat Schwann cells. Nature. 1977 Mar 24;266(5600):364–366. doi: 10.1038/266364a0. [DOI] [PubMed] [Google Scholar]
  13. Brockes J. P., Fields K. L., Raff M. C. Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve. Brain Res. 1979 Apr 6;165(1):105–118. doi: 10.1016/0006-8993(79)90048-9. [DOI] [PubMed] [Google Scholar]
  14. Bunge M. B., Bunge R. P., Peterson E. R., Murray M. R. A light and electron microscope study of long-term organized cultures of rat dorsal root ganglia. J Cell Biol. 1967 Feb;32(2):439–466. doi: 10.1083/jcb.32.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Bunge M. B. Fine structure of nerve fibers and growth cones of isolated sympathetic neurons in culture. J Cell Biol. 1973 Mar;56(3):713–735. doi: 10.1083/jcb.56.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bunge R. P., Wood P. Studies on the transplantation of spinal cord tissue in the rat. I. The development of a culture system for hemisections of embryonic spinal cord. Brain Res. 1973 Jul 27;57(2):261–276. doi: 10.1016/0006-8993(73)90135-2. [DOI] [PubMed] [Google Scholar]
  17. Bunge R., Johnson M., Ross C. D. Nature and nurture in development of the autonomic neuron. Science. 1978 Mar 31;199(4336):1409–1416. doi: 10.1126/science.24273. [DOI] [PubMed] [Google Scholar]
  18. Burger M. M. Proteolytic enzymes initiating cell division and escape from contact inhibition of growth. Nature. 1970 Jul 11;227(5254):170–171. doi: 10.1038/227170a0. [DOI] [PubMed] [Google Scholar]
  19. Carney D. H., Cunningham D. D. Initiation of check cell division by trypsin action at the cell surface. Nature. 1977 Aug 18;268(5621):602–606. doi: 10.1038/268602a0. [DOI] [PubMed] [Google Scholar]
  20. Cravioto H., Lockwood R. The bahavior of normal peripheral nerve in tissue culture. Z Zellforsch Mikrosk Anat. 1968;90(2):186–201. doi: 10.1007/BF00339429. [DOI] [PubMed] [Google Scholar]
  21. Cravioto H. The role of Schwann cells in the development of human peripheral nerves. An electron microscopic study. J Ultrastruct Res. 1965 Jun;12(5):634–651. doi: 10.1016/s0022-5320(65)80053-3. [DOI] [PubMed] [Google Scholar]
  22. De Asua L. J., Clingan D., Rudland P. S. Initiation of cell proliferation in cultured mouse fibroblasts by prostaglandin F2alpha. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2724–2728. doi: 10.1073/pnas.72.7.2724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Diner O. Les cellules de Schwann en mitose et leurs rapports avec les axones au cours du développement du nerf sciatique chez le rat. C R Acad Sci Hebd Seances Acad Sci D. 1965 Aug 18;261(7):1731–1734. [PubMed] [Google Scholar]
  24. Duffus J. H., Patterson L. J. Control of cell division in yeast using the ionophore, A23187 with calcium and magnesium. Nature. 1974 Oct 18;251(5476):626–627. doi: 10.1038/251626a0. [DOI] [PubMed] [Google Scholar]
  25. Dulbecco R., Elkington J. Induction of growth in resting fibroblastic cell cultures by Ca++. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1584–1588. doi: 10.1073/pnas.72.4.1584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Estridge M., Bunge R. Compositional analysis of growing axons from rat sympathetic neurons. J Cell Biol. 1978 Oct;79(1):138–155. doi: 10.1083/jcb.79.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Friede R. L., Johnstone M. A. Responses of thymidine labeling of nuclei in gray matter and nerve following sciatic transection. Acta Neuropathol. 1967 Jan 2;7(3):218–231. doi: 10.1007/BF00686373. [DOI] [PubMed] [Google Scholar]
  28. Gamble H. J., Breathnach A. S. An electron-microscope study of human foetal peripheral nerves. J Anat. 1965 Jul;99(Pt 3):573–584. [PMC free article] [PubMed] [Google Scholar]
  29. Gospodarowicz D., Moran J. S. Stimulation of division of sparse and confluent 3T3 cell populations by a fibroblast growth factor, dexamethasone, and insulin. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4584–4588. doi: 10.1073/pnas.71.11.4584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Green H. Cyclic AMP in relation to proliferation of the epidermal cell: a new view. Cell. 1978 Nov;15(3):801–811. doi: 10.1016/0092-8674(78)90265-9. [DOI] [PubMed] [Google Scholar]
  31. Greene W. C., Parker C. M., Parker C. W. Calcium and lymphocyte activation. Cell Immunol. 1976 Jul;25(1):74–89. doi: 10.1016/0008-8749(76)90098-8. [DOI] [PubMed] [Google Scholar]
  32. Hagopian H. K., Riggs M. G., Swartz L. A., Ingram V. M. Effect of n-butyrate on DNA synthesis in chick fibroblasts and HeLa cells. Cell. 1977 Nov;12(3):855–860. doi: 10.1016/0092-8674(77)90284-7. [DOI] [PubMed] [Google Scholar]
  33. Hanson G. R., Partlow L. M. Stimulation of non-neuronal cell proliferation in vitro by mitogenic factors present in highly purified sympathetic neurons. Brain Res. 1978 Dec 22;159(1):195–210. doi: 10.1016/0006-8993(78)90120-8. [DOI] [PubMed] [Google Scholar]
  34. Hendry I. A. Cell division in the developing sympathetic nervous system. J Neurocytol. 1977 Jun;6(3):299–309. doi: 10.1007/BF01175193. [DOI] [PubMed] [Google Scholar]
  35. Kaplowitz P. B., Moscona A. A. Lectin-mediated stimulation of DNA synthesis in cultures of embryonic neural retina cells. Exp Cell Res. 1976 Jun;100(1):177–189. doi: 10.1016/0014-4827(76)90340-2. [DOI] [PubMed] [Google Scholar]
  36. Kaplowitz P. B., Moscona A. A. Stimulation of DNA synthesis by ouabain and concanavalin A in cultures of embryonic neural retina cells. Cell Differ. 1976 Jul;5(2):109–119. doi: 10.1016/0045-6039(76)90004-x. [DOI] [PubMed] [Google Scholar]
  37. Lawson S. N., Caddy K. W., Biscoe T. J. Development of rat dorsal root ganglion neurones. Studies of cell birthdays and changes in mean cell diameter. Cell Tissue Res. 1974;153(3):399–413. doi: 10.1007/BF00229167. [DOI] [PubMed] [Google Scholar]
  38. Martin J. R., Webster H. D. Mitotic Schwann cells in developing nerve: their changes in shape, fine structure, and axon relationships. Dev Biol. 1973 Jun;32(2):417–431. doi: 10.1016/0012-1606(73)90251-0. [DOI] [PubMed] [Google Scholar]
  39. PETERS A., MUIR A. R. The relationship between axons and Schwann cells during development of peripheral nerves in the rat. Q J Exp Physiol Cogn Med Sci. 1959 Jan;44(1):117–130. doi: 10.1113/expphysiol.1959.sp001366. [DOI] [PubMed] [Google Scholar]
  40. Raff M. C., Abney E., Brockes J. P., Hornby-Smith A. Schwann cell growth factors. Cell. 1978 Nov;15(3):813–822. doi: 10.1016/0092-8674(78)90266-0. [DOI] [PubMed] [Google Scholar]
  41. Raff M. C., Hornby-Smith A., Brockes J. P. Cyclic AMP as a mitogenic signal for cultured rat Schwann cells. Nature. 1978 Jun 22;273(5664):672–673. doi: 10.1038/273672a0. [DOI] [PubMed] [Google Scholar]
  42. Romine J. S., Bray G. M., Aguayo A. J. Schwann cell multiplication after crush injury of unmyelinated fibers. Arch Neurol. 1976 Jan;33(1):49–54. doi: 10.1001/archneur.1976.00500010051008. [DOI] [PubMed] [Google Scholar]
  43. Salzer J. L., Bunge R. P., Glaser L. Studies of Schwann cell proliferation. III. Evidence for the surface localization of the neurite mitogen. J Cell Biol. 1980 Mar;84(3):767–778. doi: 10.1083/jcb.84.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Salzer J. L., Williams A. K., Glaser L., Bunge R. P. Studies of Schwann cell proliferation. II. Characterization of the stimulation and specificity of the response to a neurite membrane fraction. J Cell Biol. 1980 Mar;84(3):753–766. doi: 10.1083/jcb.84.3.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sefton B. M., Rubin H. Release from density dependent growth inhibition by proteolytic enzymes. Nature. 1970 Aug 22;227(5260):843–845. doi: 10.1038/227843a0. [DOI] [PubMed] [Google Scholar]
  46. Simpson S. A., Young J. Z. Regeneration of fibre diameter after cross-unions of visceral and somatic nerves. J Anat. 1945 Apr;79(Pt 2):48–65. [PMC free article] [PubMed] [Google Scholar]
  47. Speidel C. C. In vivo studies of myelinated nerve fibers. Int Rev Cytol. 1964;16:173–231. doi: 10.1016/s0074-7696(08)60297-1. [DOI] [PubMed] [Google Scholar]
  48. Terry L. C., Bray G. M., Aguayo A. J. Schwann cell multiplication in developing rat unmyelinated nerves-a radioautographic study. Brain Res. 1974 Mar 29;69(1):144–148. doi: 10.1016/0006-8993(74)90380-1. [DOI] [PubMed] [Google Scholar]
  49. Thomas G. A. Quantitative histology of Wallerian degeneration: II. Nuclear population in two nerves of different fibre spectrum. J Anat. 1948 Jul;82(Pt 3):135–145. [PMC free article] [PubMed] [Google Scholar]
  50. Varon S. S., Bunge R. P. Trophic mechanisms in the peripheral nervous system. Annu Rev Neurosci. 1978;1:327–361. doi: 10.1146/annurev.ne.01.030178.001551. [DOI] [PubMed] [Google Scholar]
  51. Wedner H. J., Parker C. W. Lymphocyte activation. Prog Allergy. 1976;20:195–300. [PubMed] [Google Scholar]
  52. Weinberg H. J., Spencer P. S. Studies on the control of myelinogenesis. II. Evidence for neuronal regulation of myelin production. Brain Res. 1976 Aug 27;113(2):363–378. doi: 10.1016/0006-8993(76)90947-1. [DOI] [PubMed] [Google Scholar]
  53. Weston J. A. The migration and differentiation of neural crest cells. Adv Morphog. 1970;8:41–114. doi: 10.1016/b978-0-12-028608-9.50006-5. [DOI] [PubMed] [Google Scholar]
  54. Wood P. M., Bunge R. P. Evidence that sensory axons are mitogenic for Schwann cells. Nature. 1975 Aug 21;256(5519):662–664. doi: 10.1038/256662a0. [DOI] [PubMed] [Google Scholar]
  55. Wood P. M. Separation of functional Schwann cells and neurons from normal peripheral nerve tissue. Brain Res. 1976 Oct 22;115(3):361–375. doi: 10.1016/0006-8993(76)90355-3. [DOI] [PubMed] [Google Scholar]
  56. Zetter B. R., Chen L. B., Buchanan J. M. Effects of protease treatment on growth, morphology, adhesion, and cell surface proteins of secondary chick embryo fibroblasts. Cell. 1976 Mar;7(3):407–412. doi: 10.1016/0092-8674(76)90170-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES