Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves

Nature volume 431, pages 191–195 (2004)Cite this article

Abstract

Nerve impulses are propagated at nodes of Ranvier in the myelinated nerves of vertebrates. Internodal distances have been proposed to affect the velocity of nerve impulse conduction1; however, direct evidence is lacking, and the cellular mechanisms that might regulate the length of the myelinated segments are unknown. Ramón y Cajal described longitudinal and transverse bands of cytoplasm or trabeculae in internodal Schwann cells and suggested that they had a nutritive function2. Here we show that internodal growth in wild-type nerves is precisely matched to nerve extension, but disruption of the cytoplasmic bands in Periaxin-null mice impairs Schwann cell elongation during nerve growth. By contrast, myelination proceeds normally. The capacity of wild-type and mutant Schwann cells to elongate is cell-autonomous, indicating that passive stretching can account for the lengthening of the internode during limb growth. As predicted on theoretical grounds, decreased internodal distances strikingly decrease conduction velocities and so affect motor function. We propose that microtubule-based transport in the longitudinal bands of Cajal permits internodal Schwann cells to lengthen in response to axonal growth, thus ensuring rapid nerve impulse transmission.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Longitudinal and transverse bands of Cajal in Schwann cells and their disruption in quadriceps nerve of Periaxin-null (KO) mice at 3 weeks.
Figure 2: Internodal length is decreased in Schwann cells from Prx-/- mice lacking Cajal bands.
Figure 3: The capacity of Schwann cells to specify internodal length is cell-autonomous.
Figure 4: Intact Cajal bands and microtubules are required for MBP mRNA localization at the paranodes.
Figure 5: Peripheral nerve function is compromised in Prx-/- animals.

Similar content being viewed by others

References

  1. Brill, M. H., Waxman, S. G., Moore, J. W. & Joyner, R. W. Conduction velocity and spike configuration in myelinated fibres: computed dependence on internode distance. J. Neurol. Neurosurg. Psychiatry 40, 769–774 (1977)

    Article  CAS  Google Scholar 

  2. Ramón y Cajal, S. Histology (Bailliere, Tindall & Cox, London, 1933)

    Google Scholar 

  3. Sherman, D. L., Fabrizi, C., Gillespie, C. S. & Brophy, P. J. Specific disruption of a Schwann cell dystrophin-related protein complex in a demyelinating neuropathy. Neuron 30, 677–687 (2001)

    Article  CAS  Google Scholar 

  4. Gillespie, C. S. et al. Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice. Neuron 26, 523–531 (2000)

    Article  CAS  Google Scholar 

  5. Pratt, T., Sharp, L., Nichols, J., Price, D. J. & Mason, J. O. Embryonic stem cells and transgenic mice ubiquitously expressing a tau-tagged green fluorescent protein. Dev. Biol. 228, 19–28 (2000)

    Article  CAS  Google Scholar 

  6. Ainger, K. et al. Transport and localization elements in myelin basic protein mRNA. J. Cell Biol. 138, 1077–1087 (1997)

    Article  CAS  Google Scholar 

  7. Carson, J. H., Worboys, K., Ainger, K. & Barbarese, E. Translocation of myelin basic protein mRNA in oligodendrocytes requires microtubules and kinesin. Cell Motil. Cytoskeleton 38, 318–328 (1997)

    Article  CAS  Google Scholar 

  8. Colman, D. R., Kreibich, G., Frey, A. B. & Sabatini, D. D. Synthesis and incorporation of myelin polypeptides into CNS myelin. J. Cell Biol. 95, 598–608 (1982)

    Article  CAS  Google Scholar 

  9. Griffiths, I. R. et al. Expression of myelin protein genes in Schwann cells. J. Neurocytol. 18, 345–352 (1989)

    Article  CAS  Google Scholar 

  10. Anzini, P. et al. Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin 32. J. Neurosci. 17, 4545–4551 (1997)

    Article  CAS  Google Scholar 

  11. Hursh, J. B. Conduction velocity and diameter of nerve fibers. Am. J. Physiol. 127, 131–139 (1939)

    Article  Google Scholar 

  12. Huxley, A. F. & Stampfli, R. Evidence for saltatory conduction in peripheral myelinated nerve fibres. J. Physiol. (Lond.) 108, 315–339 (1949)

    Article  Google Scholar 

  13. McIntyre, C. C., Richardson, A. G. & Grill, W. M. Modeling the excitability of mammalian nerve fibers: influence of afterpotentials on the recovery cycle. J. Neurophysiol. 87, 995–1006 (2002)

    Article  Google Scholar 

  14. Ranvier, L. Des étranglements annulaires et des segments interannulaires chez les Raies et les Torpilles. C. R. Acad. Sci. 75, 1129–1132 (1872)

    Google Scholar 

  15. Hiscoe, H. B. Distribution of nodes and incisures in normal and regenerated nerve. Anat. Rec. 99, 447–475 (1947)

    Article  CAS  Google Scholar 

  16. Schlaepfer, W. W. & Myers, F. K. Relationship of myelin internode elongation and growth in the rat sural nerve. J. Comp. Neurol. 147, 255–266 (1973)

    Article  CAS  Google Scholar 

  17. Tait, S. et al. An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction. J. Cell Biol. 150, 657–666 (2000)

    Article  CAS  Google Scholar 

  18. Komada, M. & Soriano, P. βIV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier. J. Cell Biol. 156, 337–348 (2002)

    Article  CAS  Google Scholar 

  19. Gillespie, C. S., Sherman, D. L., Blair, G. E. & Brophy, P. J. Periaxin, a novel protein of myelinating Schwann cells with a possible role in axonal ensheathment. Neuron 12, 497–508 (1994)

    Article  CAS  Google Scholar 

  20. Trapp, B. D. et al. Polarization of myelinating Schwann cell surface membranes: role of microtubules and the trans-Golgi network. J. Neurosci. 15, 1797–1807 (1995)

    Article  CAS  Google Scholar 

  21. Collinson, J. M., Marshall, D., Gillespie, C. S. & Brophy, P. J. Transient expression of neurofascin by oligodendrocytes at the onset of myelinogenesis: implications for mechanisms of axon-glial interaction. Glia 23, 11–23 (1998)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. Anderson and L. Ferguson for assistance, B. Smith for technical support, S. Scherer for comments, and K. Willeke and T. Ott of Bonn University for the CMTX mice. Figure 1a is reproduced with the permission of the Cajal Institute, CSIC, Madrid, Spain, copyright inheritors of Santiago Ramón y Cajal. This work was supported by the Wellcome Trust.

Author information

Authors and Affiliations

  1. Centre for Neuroscience Research, University of Edinburgh, EH9 1QH, Edinburgh, UK

    Felipe A. Court, Diane L. Sherman, Thomas Pratt, Emer M. Garry, Richard R. Ribchester, David F. Cottrell, Susan M. Fleetwood-Walker & Peter J. Brophy

Authors
  1. Felipe A. Court
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diane L. Sherman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Pratt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emer M. Garry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard R. Ribchester
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David F. Cottrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Susan M. Fleetwood-Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter J. Brophy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter J. Brophy.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Court, F., Sherman, D., Pratt, T. et al. Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature 431, 191–195 (2004). https://doi.org/10.1038/nature02841

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature02841

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing