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

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.

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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.

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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.

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Correspondence to Peter J. Brophy.

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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

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