Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1989 Feb 1;108(2):625–635. doi: 10.1083/jcb.108.2.625

Expression of cytotactin in the normal and regenerating neuromuscular system

PMCID: PMC2115441  PMID: 2465295

Abstract

Cytotactin is an extracellular glycoprotein found in a highly specialized distribution during embryonic development. In the brain, it is synthesized by glia, not neurons. It is involved in neuron-glia adhesion in vitro and affects neuronal migration in the developing cerebellum. In an attempt to extend these observations to the peripheral nervous system, we have examined the distribution and localization of cytotactin in different parts of the normal and regenerating neuromuscular system. In the normal neuromuscular system, cytotactin accumulated at critical sites of cell-cell interactions, specifically at the neuromuscular junction and the myotendinous junction, as well at the node of Ranvier (Rieger, F., J. K. Daniloff, M. Pincon-Raymond, K. L. Crossin, M. Grumet, and G. M. Edelman. 1986. J. Cell Biol. 103:379-391). At the neuromuscular junction, cytotactin was located in terminal nonmyelinating Schwann cells. Cytotactin was also detected near the insertion points of the muscle fibers to tendinous structures in both the proximal and distal endomysial regions of the myotendinous junctions. This was in striking contrast to staining for the neural cell adhesion molecule, N-CAM, which was accumulated near the extreme ends of the muscle fiber. Peripheral nerve damage resulted in modulation of expression of cytotactin in both nerve and muscle, particularly among the interacting tissues during regeneration and reinnervation. In denervated muscle, cytotactin accumulated in interstitial spaces and near the previous synaptic sites. Cytotactin levels were elevated and remained high along the endoneurial tubes and in the perineurium as long as muscle remained denervated. Reinnervation led to a return to normal levels of cytotactin both in inner surfaces of the nerve fascicles and in the perineurium. In dorsal root ganglia, the processes surrounding ganglionic neurons became intensely stained by anticytotactin antibodies after the nerve was cut, and returned to normal by 30 d after injury. These data suggest that local signals between neurons, glia, and supporting cells may regulate cytotactin expression in the neuromuscular system in a fashion coordinate with other cell adhesion molecules. Moreover, innervation may regulate the relative amount and distribution of cytotactin both in muscle and in Schwann cells.

Full Text

The Full Text of this article is available as a PDF (4.2 MB).

Selected References

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

  1. Chiquet-Ehrismann R., Mackie E. J., Pearson C. A., Sakakura T. Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell. 1986 Oct 10;47(1):131–139. doi: 10.1016/0092-8674(86)90374-0. [DOI] [PubMed] [Google Scholar]
  2. Chiquet M., Fambrough D. M. Chick myotendinous antigen. I. A monoclonal antibody as a marker for tendon and muscle morphogenesis. J Cell Biol. 1984 Jun;98(6):1926–1936. doi: 10.1083/jcb.98.6.1926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chiquet M., Fambrough D. M. Chick myotendinous antigen. II. A novel extracellular glycoprotein complex consisting of large disulfide-linked subunits. J Cell Biol. 1984 Jun;98(6):1937–1946. doi: 10.1083/jcb.98.6.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Covault J., Sanes J. R. Neural cell adhesion molecule (N-CAM) accumulates in denervated and paralyzed skeletal muscles. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4544–4548. doi: 10.1073/pnas.82.13.4544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crossin K. L., Hoffman S., Grumet M., Thiery J. P., Edelman G. M. Site-restricted expression of cytotactin during development of the chicken embryo. J Cell Biol. 1986 May;102(5):1917–1930. doi: 10.1083/jcb.102.5.1917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Daniloff J. K., Levi G., Grumet M., Rieger F., Edelman G. M. Altered expression of neuronal cell adhesion molecules induced by nerve injury and repair. J Cell Biol. 1986 Sep;103(3):929–945. doi: 10.1083/jcb.103.3.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edelman G. M. Cell adhesion and morphogenesis: the regulator hypothesis. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1460–1464. doi: 10.1073/pnas.81.5.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Edelman G. M. Expression of cell adhesion molecules during embryogenesis and regeneration. Exp Cell Res. 1985 Nov;161(1):1–16. doi: 10.1016/0014-4827(85)90485-9. [DOI] [PubMed] [Google Scholar]
  10. Edelman G. M. Modulation of cell adhesion during induction, histogenesis, and perinatal development of the nervous system. Annu Rev Neurosci. 1984;7:339–377. doi: 10.1146/annurev.ne.07.030184.002011. [DOI] [PubMed] [Google Scholar]
  11. Edelman G. M. Morphoregulatory molecules. Biochemistry. 1988 May 17;27(10):3533–3543. doi: 10.1021/bi00410a001. [DOI] [PubMed] [Google Scholar]
  12. Faissner A., Kruse J., Chiquet-Ehrismann R., Mackie E. The high-molecular-weight J1 glycoproteins are immunochemically related to tenascin. Differentiation. 1988;37(2):104–114. doi: 10.1111/j.1432-0436.1988.tb00802.x. [DOI] [PubMed] [Google Scholar]
  13. GUTH L. Regeneration in the mammalian peripheral nervous system. Physiol Rev. 1956 Oct;36(4):441–478. doi: 10.1152/physrev.1956.36.4.441. [DOI] [PubMed] [Google Scholar]
  14. Goujet-Zalc C., Guerci A., Dubois G., Zalc B. Schwann cell marker defined by a monoclonal antibody (224-58) with species cross-reactivity. II. Molecular characterization of the epitope. J Neurochem. 1986 Feb;46(2):435–439. doi: 10.1111/j.1471-4159.1986.tb12987.x. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Guerci A., Monge M., Baron-Van Evercooren A., Lubetzki C., Dancea S., Boutry J. M., Goujet-Zalc C., Zalc B. Schwann cell marker defined by a monoclonal antibody (224-58) with species cross-reactivity. I. Cellular localization. J Neurochem. 1986 Feb;46(2):425–434. doi: 10.1111/j.1471-4159.1986.tb12986.x. [DOI] [PubMed] [Google Scholar]
  17. Hoffman S., Crossin K. L., Edelman G. M. Molecular forms, binding functions, and developmental expression patterns of cytotactin and cytotactin-binding proteoglycan, an interactive pair of extracellular matrix molecules. J Cell Biol. 1988 Feb;106(2):519–532. doi: 10.1083/jcb.106.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hoffman S., Edelman G. M. A proteoglycan with HNK-1 antigenic determinants is a neuron-associated ligand for cytotactin. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2523–2527. doi: 10.1073/pnas.84.8.2523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ide C., Tohyama K., Yokota R., Nitatori T., Onodera S. Schwann cell basal lamina and nerve regeneration. Brain Res. 1983 Dec 12;288(1-2):61–75. doi: 10.1016/0006-8993(83)90081-1. [DOI] [PubMed] [Google Scholar]
  20. Jones F. S., Burgoon M. P., Hoffman S., Crossin K. L., Cunningham B. A., Edelman G. M. A cDNA clone for cytotactin contains sequences similar to epidermal growth factor-like repeats and segments of fibronectin and fibrinogen. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2186–2190. doi: 10.1073/pnas.85.7.2186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Linder E., Vaheri A., Ruoslahti E., Wartiovaara J. Distribution of fibroblast surface antigen in the developing chick embryo. J Exp Med. 1975 Jul 1;142(1):41–49. doi: 10.1084/jem.142.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Redshaw J. D., Bisby M. A. Comparison of the effects of sciatic nerve crush or resection on the proteins of fast axonal transport in rat dorsal root ganglion cell axons. Exp Neurol. 1985 May;88(2):437–446. doi: 10.1016/0014-4886(85)90205-5. [DOI] [PubMed] [Google Scholar]
  23. Rieger F., Daniloff J. K., Pincon-Raymond M., Crossin K. L., Grumet M., Edelman G. M. Neuronal cell adhesion molecules and cytotactin are colocalized at the node of Ranvier. J Cell Biol. 1986 Aug;103(2):379–391. doi: 10.1083/jcb.103.2.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rieger F., Grumet M., Edelman G. M. N-CAM at the vertebrate neuromuscular junction. J Cell Biol. 1985 Jul;101(1):285–293. doi: 10.1083/jcb.101.1.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rieger F., Nicolet M., Pinçon-Raymond M., Murawsky M., Levi G., Edelman G. M. Distribution and role in regeneration of N-CAM in the basal laminae of muscle and Schwann cells. J Cell Biol. 1988 Aug;107(2):707–719. doi: 10.1083/jcb.107.2.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sanes J. R., Schachner M., Covault J. Expression of several adhesive macromolecules (N-CAM, L1, J1, NILE, uvomorulin, laminin, fibronectin, and a heparan sulfate proteoglycan) in embryonic, adult, and denervated adult skeletal muscle. J Cell Biol. 1986 Feb;102(2):420–431. doi: 10.1083/jcb.102.2.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tan S. S., Crossin K. L., Hoffman S., Edelman G. M. Asymmetric expression in somites of cytotactin and its proteoglycan ligand is correlated with neural crest cell distribution. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7977–7981. doi: 10.1073/pnas.84.22.7977. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES