Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1989 Dec 1;109(6):3095–3103. doi: 10.1083/jcb.109.6.3095

Antibodies to the L1 adhesion molecule inhibit Schwann cell ensheathment of neurons in vitro

PMCID: PMC2115926  PMID: 2592417

Abstract

To investigate whether neural adhesion molecules are involved in neuron- induced Schwann cell differentiation, cocultures of pure dorsal root ganglion neurons, and Schwann cells were maintained in the presence of antibodies to evaluate possible perturbing effects. Several parameters characteristic of differentiating Schwann cells were studied, such as transition of spindle-shaped to flattened, i.e., more epithelioid morphology, association with neuronal cell bodies, ensheathment of neurites, production of basal lamina and collagen fibrils, and expression of the myelin associated glycoprotein (MAG). A complete ablation of Schwann cell differentiation in all features studied was seen with antibodies to the neural adhesion molecule L1. Antibodies to N-CAM did not reduce the association of Schwann cells with neurites but abolished the interdigitation of Schwann cell processes into neurite bundles, while leaving the other parameters studied unaffected. Fab fragments of antibodies to J1, MAG, and mouse liver membranes did not interfere with the manifestation of any of these parameters. None of the antibodies changed incorporation of [3H]thymidine into Schwann cells.

Full Text

The Full Text of this article is available as a PDF (5.0 MB).

Selected References

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

  1. 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]
  2. BORNSTEIN M. B. Reconstituted rattail collagen used as substrate for tissue cultures on coverslips in Maximow slides and roller tubes. Lab Invest. 1958 Mar-Apr;7(2):134–137. [PubMed] [Google Scholar]
  3. Barthels D., Santoni M. J., Wille W., Ruppert C., Chaix J. C., Hirsch M. R., Fontecilla-Camps J. C., Goridis C. Isolation and nucleotide sequence of mouse NCAM cDNA that codes for a Mr 79,000 polypeptide without a membrane-spanning region. EMBO J. 1987 Apr;6(4):907–914. doi: 10.1002/j.1460-2075.1987.tb04837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bixby J. L., Lilien J., Reichardt L. F. Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro. J Cell Biol. 1988 Jul;107(1):353–361. doi: 10.1083/jcb.107.1.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bunge M. B., Williams A. K., Wood P. M. Neuron-Schwann cell interaction in basal lamina formation. Dev Biol. 1982 Aug;92(2):449–460. doi: 10.1016/0012-1606(82)90190-7. [DOI] [PubMed] [Google Scholar]
  6. Bunge M. B., Williams A. K., Wood P. M., Uitto J., Jeffrey J. J. Comparison of nerve cell and nerve cell plus Schwann cell cultures, with particular emphasis on basal lamina and collagen formation. J Cell Biol. 1980 Jan;84(1):184–202. doi: 10.1083/jcb.84.1.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bunge R. P., Bunge M. B., Eldridge C. F. Linkage between axonal ensheathment and basal lamina production by Schwann cells. Annu Rev Neurosci. 1986;9:305–328. doi: 10.1146/annurev.ne.09.030186.001513. [DOI] [PubMed] [Google Scholar]
  8. Bunge R. P., Bunge M. B. Evidence that contact with connective tissue matrix is required for normal interaction between Schwann cells and nerve fibers. J Cell Biol. 1978 Sep;78(3):943–950. doi: 10.1083/jcb.78.3.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang S., Rathjen F. G., Raper J. A. Extension of neurites on axons is impaired by antibodies against specific neural cell surface glycoproteins. J Cell Biol. 1987 Feb;104(2):355–362. doi: 10.1083/jcb.104.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Faissner A., Kruse J., Nieke J., Schachner M. Expression of neural cell adhesion molecule L1 during development, in neurological mutants and in the peripheral nervous system. Brain Res. 1984 Jul;317(1):69–82. doi: 10.1016/0165-3806(84)90141-x. [DOI] [PubMed] [Google Scholar]
  11. Fischer G., Künemund V., Schachner M. Neurite outgrowth patterns in cerebellar microexplant cultures are affected by antibodies to the cell surface glycoprotein L1. J Neurosci. 1986 Feb;6(2):605–612. doi: 10.1523/JNEUROSCI.06-02-00605.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goridis C., Deagostini-Bazin H., Hirn M., Hirsch M. R., Rougon G., Sadoul R., Langley O. K., Gombos G., Finne J. Neural surface antigens during nervous system development. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 2):527–537. doi: 10.1101/sqb.1983.048.01.057. [DOI] [PubMed] [Google Scholar]
  13. Grumet M., Edelman G. M. Neuron-glia cell adhesion molecule interacts with neurons and astroglia via different binding mechanisms. J Cell Biol. 1988 Feb;106(2):487–503. doi: 10.1083/jcb.106.2.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hemperly J. J., Murray B. A., Edelman G. M., Cunningham B. A. Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM. Proc Natl Acad Sci U S A. 1986 May;83(9):3037–3041. doi: 10.1073/pnas.83.9.3037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Keilhauer G., Faissner A., Schachner M. Differential inhibition of neurone-neurone, neurone-astrocyte and astrocyte-astrocyte adhesion by L1, L2 and N-CAM antibodies. Nature. 1985 Aug 22;316(6030):728–730. doi: 10.1038/316728a0. [DOI] [PubMed] [Google Scholar]
  16. Kleitman N., Wood P., Johnson M. I., Bunge R. P. Schwann cell surfaces but not extracellular matrix organized by Schwann cells support neurite outgrowth from embryonic rat retina. J Neurosci. 1988 Feb;8(2):653–663. doi: 10.1523/JNEUROSCI.08-02-00653.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kruse J., Keilhauer G., Faissner A., Timpl R., Schachner M. The J1 glycoprotein--a novel nervous system cell adhesion molecule of the L2/HNK-1 family. Nature. 1985 Jul 11;316(6024):146–148. doi: 10.1038/316146a0. [DOI] [PubMed] [Google Scholar]
  18. Kruse J., Mailhammer R., Wernecke H., Faissner A., Sommer I., Goridis C., Schachner M. Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibodies L2 and HNK-1. Nature. 1984 Sep 13;311(5982):153–155. doi: 10.1038/311153a0. [DOI] [PubMed] [Google Scholar]
  19. Künemund V., Jungalwala F. B., Fischer G., Chou D. K., Keilhauer G., Schachner M. The L2/HNK-1 carbohydrate of neural cell adhesion molecules is involved in cell interactions. J Cell Biol. 1988 Jan;106(1):213–223. doi: 10.1083/jcb.106.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lemke G., Axel R. Isolation and sequence of a cDNA encoding the major structural protein of peripheral myelin. Cell. 1985 Mar;40(3):501–508. doi: 10.1016/0092-8674(85)90198-9. [DOI] [PubMed] [Google Scholar]
  21. Leutz A., Schachner M. Epidermal growth factor stimulates DNA-synthesis of astrocytes in primary cerebellar cultures. Cell Tissue Res. 1981;220(2):393–404. doi: 10.1007/BF00210517. [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. Martini R., Schachner M. Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and MAG) and their shared carbohydrate epitope and myelin basic protein in developing sciatic nerve. J Cell Biol. 1986 Dec;103(6 Pt 1):2439–2448. doi: 10.1083/jcb.103.6.2439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Martini R., Schachner M. Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and myelin-associated glycoprotein) in regenerating adult mouse sciatic nerve. J Cell Biol. 1988 May;106(5):1735–1746. doi: 10.1083/jcb.106.5.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Moos M., Tacke R., Scherer H., Teplow D., Früh K., Schachner M. Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin. Nature. 1988 Aug 25;334(6184):701–703. doi: 10.1038/334701a0. [DOI] [PubMed] [Google Scholar]
  26. Owens G. C., Bunge R. P. Evidence for an early role for myelin-associated glycoprotein in the process of myelination. Glia. 1989;2(2):119–128. doi: 10.1002/glia.440020208. [DOI] [PubMed] [Google Scholar]
  27. PORTER R. R. The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem J. 1959 Sep;73:119–126. doi: 10.1042/bj0730119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pollerberg G. E., Schachner M., Davoust J. Differentiation state-dependent surface mobilities of two forms of the neural cell adhesion molecule. Nature. 1986 Dec 4;324(6096):462–465. doi: 10.1038/324462a0. [DOI] [PubMed] [Google Scholar]
  29. Poltorak M., Sadoul R., Keilhauer G., Landa C., Fahrig T., Schachner M. Myelin-associated glycoprotein, a member of the L2/HNK-1 family of neural cell adhesion molecules, is involved in neuron-oligodendrocyte and oligodendrocyte-oligodendrocyte interaction. J Cell Biol. 1987 Oct;105(4):1893–1899. doi: 10.1083/jcb.105.4.1893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rathjen F. G., Schachner M. Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J. 1984 Jan;3(1):1–10. doi: 10.1002/j.1460-2075.1984.tb01753.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ratner N., Bunge R. P., Glaser L. A neuronal cell surface heparan sulfate proteoglycan is required for dorsal root ganglion neuron stimulation of Schwann cell proliferation. J Cell Biol. 1985 Sep;101(3):744–754. doi: 10.1083/jcb.101.3.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Sadoul K., Sadoul R., Faissner A., Schachner M. Biochemical characterization of different molecular forms of the neural cell adhesion molecule L1. J Neurochem. 1988 Feb;50(2):510–521. doi: 10.1111/j.1471-4159.1988.tb02941.x. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Seilheimer B., Persohn E., Schachner M. Neural cell adhesion molecule expression is regulated by Schwann cell-neuron interactions in culture. J Cell Biol. 1989 May;108(5):1909–1915. doi: 10.1083/jcb.108.5.1909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Seilheimer B., Schachner M. Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture. J Cell Biol. 1988 Jul;107(1):341–351. doi: 10.1083/jcb.107.1.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Weinberg H. J., Spencer P. S. Studies on the control of myelinogenesis. I. Myelination of regenerating axons after entry into a foreign unmyelinated nerve. J Neurocytol. 1975 Aug;4(4):395–418. doi: 10.1007/BF01261372. [DOI] [PubMed] [Google Scholar]

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

RESOURCES