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. 1998 Aug;193(Pt 2):195–201. doi: 10.1046/j.1469-7580.1998.19320195.x

A strong myelin thickness-axon size correlation emerges in developing nerves despite independent growth of both parameters

J FRAHER 1,✉, P DOCKERY 1
PMCID: PMC1467839  PMID: 9827635

Abstract

The axon determines whether or not it is myelinated by the Schwann cell. At maturity there is a positive correlation between sheath thickness and axon calibre. This correlation is initially very low or absent, but gradually strengthens during development. This increase could come about because the axon continuously controls Schwann cell myelinating activity, so that a given axon calibre is associated with a particular myelin sheath thickness, an interaction which would entail the Schwann cell continuously monitoring and responding to axon size. This seems unnecessarily complex. This theoretical study shows that the strong correlation between the 2 parameters within a given myelinated fibre population may come about in a much simpler way than outlined above. This is demonstrated by modelling the growth and myelination of a hypothetical population, utilising data from earlier studies on cervical ventral motoneuron axon development. The hypothesis tested shows that the only instructive interactions by the axon on the Schwann cell necessary for the strong correlation between the 2 parameters to emerge are for the initiation of myelination, its continuation and its termination. These could result from a single stimulus being switched on, persisting for a time and being switched off. Under this influence, the Schwann cell is assumed to proceed to form the myelin sheath at a constant rate which it itself inherently determines, in the absence of any quantitative influence exerted by the axon. This continues until the stimulus for myelination ceases to emanate from the axon. The validity of the hypothesis is demonstrated, because the resulting myelin-axon relationships correspond closely to those observed during development.

Keywords: Peripheral nerve, myelinogenesis, axon-glial interactions

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Selected References

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  1. Aguayo A. J., Charron L., Bray G. M. Potential of Schwann cells from unmyelinated nerves to produce myelin: a quantitative ultrastructural and radiographic study. J Neurocytol. 1976 Oct;5(8):565–573. doi: 10.1007/BF01175570. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Biscoe T. J., Nickels S. M., Stirling C. A. Numbers and sizes of nerve fibres in mouse spinal roots. Q J Exp Physiol. 1982 Jul;67(3):473–494. doi: 10.1113/expphysiol.1982.sp002663. [DOI] [PubMed] [Google Scholar]
  4. Colello R. J., Pott U. Signals that initiate myelination in the developing mammalian nervous system. Mol Neurobiol. 1997 Aug;15(1):83–100. doi: 10.1007/BF02740617. [DOI] [PubMed] [Google Scholar]
  5. Fraher J. P. A numerical study of cervical and thoracic ventral nerve roots. J Anat. 1974 Sep;118(Pt 1):127–142. [PMC free article] [PubMed] [Google Scholar]
  6. Fraher J. P. A quantitative study of anterior root fibres during early myelination. II. Longitudinal variation in sheath thickness and axon circumference. J Anat. 1973 Sep;115(Pt 3):421–444. [PMC free article] [PubMed] [Google Scholar]
  7. Fraher J. P. A quantitative study of anterior root fibres during early myelination. J Anat. 1972 May;112(Pt 1):99–124. [PMC free article] [PubMed] [Google Scholar]
  8. Fraher J. P. Axon-myelin relationships in rat cranial nerves III, IV, and VI: a morphometric study of large- and small-fibre classes. J Comp Neurol. 1989 Aug 15;286(3):384–390. doi: 10.1002/cne.902860308. [DOI] [PubMed] [Google Scholar]
  9. Fraher J. P., Kaar G. F., Bristol D. C., Rossiter J. P. Development of ventral spinal motoneurone fibres: a correlative study of the growth and maturation of central and peripheral segments of large and small fibre classes. Prog Neurobiol. 1988;31(3):199–239. doi: 10.1016/0301-0082(88)90035-4. [DOI] [PubMed] [Google Scholar]
  10. Fraher J. P., Kaar G. F. The development of alpha and gamma motoneuron fibres in the rat. II. A comparative ultrastructural study of their central and peripheral myelination. J Anat. 1985 Aug;141:89–103. [PMC free article] [PubMed] [Google Scholar]
  11. Fraher J. P. Myelin-axon relationships in the rat phrenic nerve: longitudinal variation and lateral asymmetry. J Comp Neurol. 1992 Sep 22;323(4):551–557. doi: 10.1002/cne.903230407. [DOI] [PubMed] [Google Scholar]
  12. Fraher J. P., O'Sullivan V. R. Age changes in axon number along the cervical ventral spinal nerve roots in rats. J Comp Neurol. 1989 Feb 8;280(2):171–182. doi: 10.1002/cne.902800202. [DOI] [PubMed] [Google Scholar]
  13. Fraher J. P. Quantitative studies on the maturation of central and peripheral parts of individual ventral motoneuron axons. I. Myelin sheath and axon calibre. J Anat. 1978 Aug;126(Pt 3):509–533. [PMC free article] [PubMed] [Google Scholar]
  14. Fraher J. P. Quantitative studies on the maturation of central and peripheral parts of individual ventral motoneuron axons. II. Internodal length. J Anat. 1978 Sep;127(Pt 1):1–15. [PMC free article] [PubMed] [Google Scholar]
  15. Fraher J. P. The growth and myelination of central and peripheral segments of ventral motoneurone axons. A quantitative ultrastructural study. Brain Res. 1976 Mar 26;105(2):193–211. doi: 10.1016/0006-8993(76)90421-2. [DOI] [PubMed] [Google Scholar]
  16. Friede R. L., Bischhausen R. How are sheath dimensions affected by axon caliber and internode length? Brain Res. 1982 Mar 11;235(2):335–350. doi: 10.1016/0006-8993(82)91012-5. [DOI] [PubMed] [Google Scholar]
  17. Friede R. L., Brzoska J., Hartmann U. Changes in myelin sheath thickness and internode geometry in the rabbit phrenic nerve during growth. J Anat. 1985 Dec;143:103–113. [PMC free article] [PubMed] [Google Scholar]
  18. Friede R. L. Control of myelin formation by axon caliber (with a model of the control mechanism). J Comp Neurol. 1972 Feb;144(2):233–252. doi: 10.1002/cne.901440207. [DOI] [PubMed] [Google Scholar]
  19. Friede R. L., Samorajski T. Myelin formation in the sciatic nerve of the rat. A quantitative electron microscopic, histochemical and radioautographic study. J Neuropathol Exp Neurol. 1968 Oct;27(4):546–570. [PubMed] [Google Scholar]
  20. Friede R. L., Samorajski T. Relation between the number of myelin lamellae and axon circumference in fibers of vagus and sciatic nerves of mice. J Comp Neurol. 1967 Jul;130(3):223–231. doi: 10.1002/cne.901300304. [DOI] [PubMed] [Google Scholar]
  21. Hildebrand C., Hahn R. Relation between myelin sheath thickness and axon size in spinal cord white matter of some vertebrate species. J Neurol Sci. 1978 Oct;38(3):421–434. doi: 10.1016/0022-510x(78)90147-8. [DOI] [PubMed] [Google Scholar]
  22. Jacobs J. M. On internodal length. J Anat. 1988 Apr;157:153–162. [PMC free article] [PubMed] [Google Scholar]
  23. Jessen K. R., Mirsky R., Morgan L. Axonal signals regulate the differentiation of non-myelin-forming Schwann cells: an immunohistochemical study of galactocerebroside in transected and regenerating nerves. J Neurosci. 1987 Oct;7(10):3362–3369. doi: 10.1523/JNEUROSCI.07-10-03362.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jessen K. R., Mirsky R., Morgan L. Myelinated, but not unmyelinated axons, reversibly down-regulate N-CAM in Schwann cells. J Neurocytol. 1987 Oct;16(5):681–688. doi: 10.1007/BF01637659. [DOI] [PubMed] [Google Scholar]
  25. Jessen K. R., Mirsky R. Schwann cell precursors and their development. Glia. 1991;4(2):185–194. doi: 10.1002/glia.440040210. [DOI] [PubMed] [Google Scholar]
  26. Kaar G. F., Fraher J. P. The development of alpha and gamma motoneuron fibres in the rat. I. A comparative ultrastructural study of their central and peripheral axon growth. J Anat. 1985 Aug;141:77–88. [PMC free article] [PubMed] [Google Scholar]
  27. Low M. G. The glycosyl-phosphatidylinositol anchor of membrane proteins. Biochim Biophys Acta. 1989 Dec 6;988(3):427–454. doi: 10.1016/0304-4157(89)90014-2. [DOI] [PubMed] [Google Scholar]
  28. Low P. A. Hereditary hypertrophic neuropathy in the trembler mouse. Part 2. Histopathological studies: electron microscopy. J Neurol Sci. 1976 Dec;30(2-3):343–368. doi: 10.1016/0022-510x(76)90139-8. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Martini R., Xin Y., Schmitz B., Schachner M. The L2/HNK-1 Carbohydrate Epitope is Involved in the Preferential Outgrowth of Motor Neurons on Ventral Roots and Motor Nerves. Eur J Neurosci. 1992;4(7):628–639. doi: 10.1111/j.1460-9568.1992.tb00171.x. [DOI] [PubMed] [Google Scholar]
  31. Murray J. A., Blakemore W. F. The relationship between internodal length and fibre diameter in the spinal cord of the cat. J Neurol Sci. 1980 Feb;45(1):29–41. doi: 10.1016/s0022-510x(80)80004-9. [DOI] [PubMed] [Google Scholar]
  32. Schröder J. M., Bohl J., Brodda K. Changes of the ratio between myelin thickness and axon diameter in the human developing sural nerve. Acta Neuropathol. 1978 Aug 7;43(1-2):169–178. doi: 10.1007/BF00685012. [DOI] [PubMed] [Google Scholar]
  33. Smith K. J., Blakemore W. F., Murray J. A., Patterson R. C. Internodal myelin volume and axon surface area. A relationship determining myelin thickness? J Neurol Sci. 1982 Aug;55(2):231–246. doi: 10.1016/0022-510x(82)90103-4. [DOI] [PubMed] [Google Scholar]
  34. THOMAS P. K., YOUNG J. Z. Internode lengths in the nerves of fishes. J Anat. 1949 Oct;83(4):336-50, pl. [PMC free article] [PubMed] [Google Scholar]
  35. Vizoso A. D., Young J. Z. Internode length and fibre diameter in developing and regenerating nerves. J Anat. 1948 Apr;82(Pt 1-2):110–134.1. [PMC free article] [PubMed] [Google Scholar]
  36. Voyvodic J. T. Target size regulates calibre and myelination of sympathetic axons. Nature. 1989 Nov 23;342(6248):430–433. doi: 10.1038/342430a0. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Weinberg H. J., Spencer P. S. Studies on the control of myelinogenesis. II. Evidence for neuronal regulation of myelin production. Brain Res. 1976 Aug 27;113(2):363–378. doi: 10.1016/0006-8993(76)90947-1. [DOI] [PubMed] [Google Scholar]
  39. Williams P. L., Wendell-Smith C. P. Some additional parametric variations between peripheral nerve fibre populations. J Anat. 1971 Sep;109(Pt 3):505–526. [PMC free article] [PubMed] [Google Scholar]

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