Skip to main content
Log in

Terminal Schwann cells elaborate extensive processes following denervation of the motor endplate

  • Published:
Journal of Neurocytology

Summary

Terminal Schwann cells, when stained for S100 (a calcium binding protein), can be seen to cap motor axons at the neuromuscular junction. Within days of denervation the Schwann cells begin to stain for the low affinity nerve growth factor receptor, but remain Thy-1 negative, and elaborate fine processes. These processes become longer and more disorganized over weeks, and cells positive for S100 and nerve growth factor receptor migrate into the perisynaptic area. Reinnervation results in a withdrawal of the processes. The morphology and location of terminal Schwann cells seems to depend on axonal contact. The spread of Schwann cells and their processes away from the synaptic zone following denervation, implies that these cells do not target axons directly to the endplate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aguayo, A. J., Epps, J., Charron, L. &Bray, G. M. (1976) Multipotentiality of Schwann cells in cross-anastomsis and graft in myelinated and unmyelinated nerves: quantitative microscopy and radioautography.Brain Research 104, 1–20.

    PubMed  Google Scholar 

  • Alderson, K., Pestronk, A., Woon-Che, Y. &Drachman, D. B. (1989) Silver cholinesterase immunocytochemistry: a new neuromuscular junction stain.Muscle & Nerve 12, 9–14.

    Google Scholar 

  • Ard, M. D., Bunge, R. P. &Bunge, M. B. (1987) Comparison of the Schwann cell surface and Schwann cell extracellular matrix as promoters of neurite growth.Journal of Neurocytology 16, 539–57.

    PubMed  Google Scholar 

  • Baichwal, R. R., Bigbee, J. W. &De Vries, G. H. (1988) Macrophage-mediated myelin related mitogenic factor from cultured Schwann cells.Proceedings of the National Academy of Sciences (USA) 85, 1701–5.

    Google Scholar 

  • Bignami, A., Dahl, D., Nguyen, B. T. &Crosby, C. J. (1981) The fate of axonal debris in Wallerian degeneration of rat optic and sciatic nerves. Electron microscopy and immunofluorescence studies with neurofilament antisera.Journal of Neuropathology & Experimental Neurology 40, 537–50.

    Google Scholar 

  • Bignami, A., Chi, N. H. &Dahl, D. (1984) Laminin in rat sciatic nerve undergoing Wallerian degeneration.Journal of Neuropathology and Experimental Neurohgy 43, 94–103.

    Google Scholar 

  • Billings-Gagliardi, S., Webster, H. De F. &O'Connell, M. F. (1974)In vivo and electronmicroscopic observation on Schwann cells in developing tadpole nerve fibres.American Journal of Anatomy 141, 375–92.

    PubMed  Google Scholar 

  • Bixby, J. L., Pratt, R. S., Lilien, J. &Reichardt, L. F. (1987) Neurite outgrowth on muscle cell surfaces involves extracellular matrix receptors as well as Ca2+-dependent and -independent cell adhesion molecules.Proceedings of the National Academy of Sciences (USA) 84, 2555–9.

    Google Scholar 

  • Bixby, J. L., Lillien, J. &Reichardt, L. F. (1988) Identification of the major proteins that promote neuronal process outgrowth on Schwann cellsin vitro.Journal of Cell Biology 107, 353–61.

    Google Scholar 

  • Brockes, J. P., Fields, K. L. &Raff, M. C. (1977) A surface antigenic marker for rat Schwann cells.Nature 266, 364–6.

    PubMed  Google Scholar 

  • Brockes, J. P., Fields, K. L. &Raff, M. C. (1979) Studies on cultured rat Schwann cells. 1. Establishment of purified population for cultures of rat peripheral nerve.Brain Research 165, 105–18.

    PubMed  Google Scholar 

  • Brown, M. C., Holland, R. L. &Hopkins, W. G. (1981) Motor nerve sprouting.Annual Review of Neuroscience 4, 17–42.

    PubMed  Google Scholar 

  • Bunge, M. B., Williams, A. K. &Wood, P. M. (1982) Neuron-Schwann cell interaction in basai lamina formation.Developmental Biology 92, 449–60.

    PubMed  Google Scholar 

  • Caroni, P. &Grandes, P. (1990) Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors.Journal of Cell Biology 110, 1307–17.

    Google Scholar 

  • Chandler, C. E., Parsons, L. M., Hosang, M. &Shooter, E. M. (1984) A monoclonal antibody modulates the interaction of nerve growth factor with PC 12 cells.Journal of Biological Chemistry 259, 6882–9.

    Google Scholar 

  • Clark, M. B. &Bunge, M. B. (1989) Cultured Schwann cells assemble normal-appearing basal lamina only when they ensheath axons.Developmental Biology 133, 393–404.

    PubMed  Google Scholar 

  • Cocchia, D. &Michetti, F. (1981) S-100 antigen in satellite cells of the adrenal medulla and the superior cervical ganglion of the rat. An immunochemical and immuno-cytochemical study.Cell and Tissue Research 215, 103–112.

    PubMed  Google Scholar 

  • Connor, E. A. &Mcmahan, U. J. (1987) Cell accumulation in the junctional region of denervated muscle.Journal of Cell Biology 104, 109–20.

    PubMed  Google Scholar 

  • Covault, J. &Sanes, J. R. (1985) Neural cell adhesion molecule (N-CAM) accumulates in denervated and paralysed skeletal muscle.Proceedings of the National Academy of Sciences (USA) 82, 4544–8.

    Google Scholar 

  • Covault, J., Cunningham, J. M. &Sanes, J. R. (1987) Neurite outgrowth on cryostat sections of innervated and denervated skeletal muscle.Journal of Cell Biology 105, 2479–88.

    Google Scholar 

  • De Koning, P. &Gispen, W. H. (1987) Org.2766 improves functional and electrophysiological aspects of regenerating sciatic nerve in the rat.Peptides 8, 415–22.

    PubMed  Google Scholar 

  • Fadic, R., Brandan, E. &Inestrsa, N. C. (1990) Motor nerve regulates muscle extracellular matrix proteoglycan expression.Journal of Neuroscience 10, 3516–23.

    PubMed  Google Scholar 

  • Fallon, J. R. (1985) Preferential outgrowth of central nervous system neurites on astrocytes and Schwann cells as compared with non-glial cellsin vitro.Journal of Cell Biology 100, 198–207.

    PubMed  Google Scholar 

  • Fawcett, J. W. &Keynes, R. J. (1990) Peripheral nerve regeneration.Annual Review of Neuroscience 13, 43–60.

    PubMed  Google Scholar 

  • Gatchalian, C. L., Schachner, M. &Sanes, J. R. (1989) Fibroblasts that proliferate near denervated synaptic sites in skeletal muscle synthesize the adhesive molecules tenascin (J1), N-CAM, fibronectin, and a heparin sulfate proteoglycan.Journal of Cell Biology 108, 1873–90.

    Google Scholar 

  • Gibson, S. J., Folak, J. M., Bloom, S. R., Sabate, I. M., Mulderry, P. M., Ghatei, M. A., Mcgregor, S. P., Morrison, J. F. B., Kelly, J. S., Evans, R. M. &Rosenfeld, M. G. (1984) Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and eight other species.Journal of Neuroscience 4, 3101–11.

    Google Scholar 

  • Gorio, A., Carmignoto, G., Finesso, M., Polato, P. &Nunzi, M. G. (1983) Muscle reinnervation-II. Sprouting, synapse formation and repression.Neuroscience 8, 403–15.

    PubMed  Google Scholar 

  • Gutman, E. &Young, J. Z. (1944) The reinnervation of muscle after various periods of atrophy.Journal of Anatomy 78, 15–43.

    Google Scholar 

  • Henderson, C. E., Huchet, M. &Changeux, J. P. (1983) Denervation increases a neurite-promoting activity in extracts of skeletal muscle.Nature 302, 609–11.

    PubMed  Google Scholar 

  • Heumann, R., Lindholm, D., Bandtlow, C., Meyer, M., Radeke, M. J., Misko, T. P., Shooter, E. &Thoenen, H. (1987a) Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development degeneration and regeneration: Role of macrophages.Proceedings of the National Academy of Sciences (USA) 84, 8735–9.

    Google Scholar 

  • Heumann, R., Korsching, S., Bandtlow, C. &Thoenen, H. (1987b) Changes in nerve growth factor synthesis in response to sciatic nerve transectionJournal of Cell Biology 104, 1623–31.

    PubMed  Google Scholar 

  • Hunter, D. D., Shah, U., Merlic, J. P. &Sanes, J. R. (1989) A lamin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction.Nature 338, 229–34.

    PubMed  Google Scholar 

  • Ide, C., Tohyama, K., Yokota, R., Nitatori, T. &Onodera, S. (1983) Schwann cell basal lamina and nerve regeneration.Brain Research 288, 61–75.

    PubMed  Google Scholar 

  • Isobe, T., Takahashi, K. &Okuyama, T. (1984) S-100ao (alpha, alpha) protein is present in neurons of the central and peripheral nervous system.Journal of Neurochemistry 43, 1494–6.

    Google Scholar 

  • Jacobson, S. &Guth, L. (1965) An electrophysiological study of the early stages of peripheral nerve regeneration.Experimental Neurology 11, 48–56.

    PubMed  Google Scholar 

  • Jessen, K. R., Morgan, L., Brammer, M. &Mirsky, R. (1985) Galactocerebroside is expressed by non-myelin forming Schwann cellsin situ.Journal of Cell Biology 101, 1135–43.

    PubMed  Google Scholar 

  • Jessen, K. R., Mirsky, R. &Morgan, L. (1987) Myelinated but not unmyelinated axons, reversibly down-regulate N-CAM in Schwann cells.Journal of Neurocytology 16, 681–8.

    PubMed  Google Scholar 

  • Jessen, K. R., Morgan, L., Stewart, H. J. S. &Mirsky, R. (1990) Three markers of adult non-myelin forming Schwann cells, 217c(Ran-1), A5E3 and GFAP: development and regulation by neuron-Schwann cell interactions.Development 109, 91–103.

    PubMed  Google Scholar 

  • Keynes, R. J., Hopkins, W. G. &Brown, M. C. (1983) Sprouting of mammalian motorneurones at nodes of Ranvier: the role of the denervated motor endplate.Brain Research 264, 209–13.

    PubMed  Google Scholar 

  • Kligman, D. &Hilt, D. C. (1988) The S100 protein family.Trends in Biochemical Sciences 13, 437–443.

    PubMed  Google Scholar 

  • Kuffler, D. P. (1989) Regeneration of muscle axons in the frog is directed by diffusible factors from denervated muscle.Journal of Comparative Neurology 281, 416–25.

    PubMed  Google Scholar 

  • Lander, A. D., Fujii, D. K. &Reichardt, L. F. (1985) Laminin is associated with the ‘neurite outgrowthpromoting factors’ found in conditioned media.Proceedings of the National Academy of Sciences (USA) 82, 2183–7.

    Google Scholar 

  • Lubinska, L. (1977) Early course of Wallerin degeneration in myelinated fibres of the rat phrenic nerve.Brain Research 130, 47–63.

    PubMed  Google Scholar 

  • Manolov, S. (1974) Initial changes in the neuromuscular synapses of denervated rat diaphragm.Brain Research 65, 303–16.

    PubMed  Google Scholar 

  • Manthorpe, M., Engvall, E., Ruoslahti, E., Longo, F., Davis, G. &Varon, S. (1983) Lamina promotes neuritic regeneration from cultured peripheral and central neurons.Journal of Cell Biology 97, 1882–90.

    Google Scholar 

  • Marshall, L. M., Sanes, J. R. &Mcmahan, U. J. (1977) Reinnervation of original synaptic sites on muscle fibre basement membrane after disruption of the muscle cells.Proceedings of the National Academy of Sciences (USA) 74, 3073–77.

    Google Scholar 

  • Mata, M., Alessi, D. &Fink, D. J. (1990) S100 is preferentially distributed in myelin-forming Schwann cells.Journal of Neurocytology 19, 432–42.

    Google Scholar 

  • Matteoli, M., Haimann, C., Torri-Tarelli, F., Polak, J. M., Ceccarelli, B. &De Camilli, P. (1988) Differential effect of α-latrotoxin on exocytosis from small synaptic vesicles and from large dense core vesicles containing calcitonin gene-related peptide of the frog neuromuscular junction.Proceedings of the National Academy of Sciences (USA) 85, 7366–70.

    Google Scholar 

  • Mclean, I. W. &Nakane, P. K. (1974) Periodate-lysine-paraformaldehyde fixative. A new fixative for immunoelectron microscopy.Journal of Histochemistry and Cytochemistry 22, 1077–83.

    PubMed  Google Scholar 

  • Mcmahan, U. J., Sanes, J. R. &Marshall, L. M. (1978) Cholinesterase is associated with the basal lamina at the neuromuscular junction.Nature 193, 281–2.

    Google Scholar 

  • Mcquarrie, I. G., Grafstein, B. &Gershon, M. D. (1977) Axonal regeneration in the rat sciatic nerve: effects of a conditioning lesion and of dbcAMP.Brain Research 132, 443–52.

    PubMed  Google Scholar 

  • Miledi, R. &Slater, C. R. (1970) On the degeneration of rat neuromuscular junctions after nerve section.Journal of Physiology 207, 507–28.

    PubMed  Google Scholar 

  • Miller, F. D., Tetzlaff, W., Bisby, M. A., Fawcett, J. W. &Milner, R. J. (1989) Rapid induction of the major embryonic tubulin mRNA, T1 during nerve regeneration in rats.Journal of Neuroscience 9, 1452–63.

    PubMed  Google Scholar 

  • Mirsky, R., Winter, J., Abney, E. R., Pruss, R. M., Gavrilovic, J. &Raff, M. C. (1980) Myelin-specific proteins and glycolipids in rat Schwann cells and oligodendrocytes in culture.Journal of Cell Biology 84, 483–94.

    PubMed  Google Scholar 

  • Mora, M., Marchi, M., Polak, J. M., Gibson, S. J. &Cornelio, F. (1989) Calcitonin gene-related peptide immunoreactivity at the human neuromuscular junction.Brain Research 492, 404–7.

    PubMed  Google Scholar 

  • Murray, M. A. &Robbins, N. (1982) Cell proliferation in denervated muscle: identity and origin of the dividing cells.Neuroscience 7, 1823–34.

    PubMed  Google Scholar 

  • Neuberger, T. J. &Cornbrooks, C. J. (1989) Transient modulation of Schwarm cell antigens after peripheral nerve transection and subsequent regeneration.Journal of Neurocytology 18, 695–710.

    PubMed  Google Scholar 

  • Payer, A. F. (1979) An ultrastructural study of Schwann cell response to axonal degeneration.Journal of Comparative Neurology 183, 365–84.

    PubMed  Google Scholar 

  • Ramon Y Cajal, S. (1928) (trans. 1959). Degeneration and regeneration of the nervous system (edited and translated byR. M. May) New York: Hafner Publishing Company.

    Google Scholar 

  • Reiger, F., Frumet, M. &Edelman, G. M. (1985) N-CAM at the vertebrate neuromuscular junction.Journal of Cell Biology 101, 285–93.

    Google Scholar 

  • Rich, M. M. &Lichtman, J. W. (1989) In vivo visualization of pre- and postsynaptic changes during synapse elimination in reinnervated mouse muscle.Journal of Neuroscience 9, 1781–1805.

    PubMed  Google Scholar 

  • Sanes, J. R. (1989) Extracellular matrix molecules that influence neural development.Annual Review of Neuroscience 12, 521–46.

    Google Scholar 

  • Sanes, J. R. &Covault, J. (1985) Axon guidance during reinnervation of skeletal muscle.Trends in Neuroscience 8, 523–8.

    Google Scholar 

  • Sanes, J. R., Marshall, L. M. &Mcmahan, U. J. (1978) Reinnervation of muscle fibre basal lamina after removal of myofibres. Differentiation of regenerating axons at original synaptic sites.Journal of Cell Biology 78, 176–98.

    PubMed  Google Scholar 

  • Sanes, J. R., Schachner, M. &Covault, J. (1986) Expression of several adhesion macromolecules in embryonic, adult, and denervated adult skeletal muscle.Journal of Cell Biology 102, 420–31.

    Google Scholar 

  • Seilheimer, B. &Schachner, M. (1988) Studies of adhesion molecules mediating interaction between cells of the peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture.Journal of Cell Biology 107, 341–51.

    Google Scholar 

  • Skene, H. J. P. (1989) Axonal growth-associated proteins.Annual Review of Neuroscience 12, 127–56.

    PubMed  Google Scholar 

  • Spreca, A., Rambotti, M. G., Rende, M., Saccardi, C., Aisa, M. L., Gianbanco, I. &Donato, R. (1989) Immunocytochemical localization of S-100b protein in degenerating and regenerating rat sciatic nerves.Journal of Histochemistry and Cytochemistry 37, 441–6.

    PubMed  Google Scholar 

  • Stefansson, K., Wollmann, R. L. &Moore, B. W. (1982) Distribution of S-100 protein outside the central nervous system.Brain Research 234, 309–17.

    PubMed  Google Scholar 

  • Streit, W. J., Dumoulin, F. L., Raivich, &Kreutzberg, G. W. (1989) Calcitonin gene-related peptide increases in rat facial motoneurons after peripheral nerve transection.Neuroscience Letters 101, 143–8.

    PubMed  Google Scholar 

  • Stemple, D. L. &Anderson, D. J. (1991) A Schwann Cell antigen recognized by monoclonal antibody 217c is the low-affinity nerve growth receptor.Neuroscience Letters 124, 57–60.

    PubMed  Google Scholar 

  • Sugimura, K., Haimoto, H., Nagura, H., Kato, K. &Takahashi, A. (1989) Immunohistochemical differential distribution of S-100a and S100b in the peripheral nervous system of the rat.Muscle and Nerve 12, 929–35.

    PubMed  Google Scholar 

  • Sunderland, S. (1978)Nerves and Nerve Injuries. 2nd ed. Edinburgh: Churchill Livingstone.

    Google Scholar 

  • Taniuchi, M., Clark, H. B. &Johnson, E. M. (1986) Induction of nerve growth factor receptor in Schwann cells after axotomy.Proceedings of the National Academy of Sciences (USA) 83, 4094–8.

    Google Scholar 

  • Taniuchi, M., Clark, H. B., Schweitzer, J. B. &Johnson, E. M. (1988) Expression of nerve growth factor receptors by Schwann cells of axotomized peripheral nerves: ultrastructural localization, suppression by axonal contact and binding properties.Journal of Neuroscience 8, 664–81.

    PubMed  Google Scholar 

  • Terenghi, G., Polak, J. M., Rodrigo, J., Mulderry, P. K. &Bloom, S. R. (1986) Calcitonin gene-related peptide-immunoreactive nerves in the tongue, epiglottis and pharynx of the rat: occurrence, distribution and origin.Brain Research 365, 1–14.

    PubMed  Google Scholar 

  • Traub, R. J., Iadarola, M. J. &Ruda, M. A. (1989) Effect of multiple dorsal rhizotomies on calcitonin gene-related peptide-like immunoreactivity in the lumbosacral dorsal spinal cord of the cat: a radioimmunoassay analysis.Peptides 10, 979–83.

    PubMed  Google Scholar 

  • Wong, J. &Oblinger, M. M. (1990) A comparison of peripheral and central axotomy effects on neurofilament and tubulin gene expression in rat dorsal root ganglion neurons.Journal of Neuroscience 10, 2215–22.

    PubMed  Google Scholar 

  • Zuber, M. X., Goodman, D. W., Karns, L. R. &Fishman, M. C. (1989) The neuronal growth-associated protein GAP-43 induces filopodia in non-neuronal cells.Science 244, 1193–5.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reynolds, M.L., Woolf, C.J. Terminal Schwann cells elaborate extensive processes following denervation of the motor endplate. J Neurocytol 21, 50–66 (1992). https://doi.org/10.1007/BF01206897

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01206897

Keywords

Navigation