Neurofilament gene expression: A major determinant of axonal caliber

P. N. Hoffman, D. W. Cleveland, J. W. Griffin, P. W. Landes, N. J. Cowan, D. L. Price

Research output: Contribution to journalArticle

Abstract

Within the wide spectrum of axonal diameters occurring in mammalian nerve fibers, each class of neurons has a relatively restricted range of axonal calibers. The control of caliber has functional significance because diameter is the principal determinant of conduction velocity in myelinated nerve fibers. Previous observations support the hypothesis that neurofilaments (NF) are major intrinsic determinants of axonal caliber in large myelinated nerve fibers. Following interruption of axons (axotomy) by crushing or cutting a peripheral nerve, caliber is reduced in the proximal axonal stumps, which extend from the cell bodies to the site of axotomy. (The distal axonal stumps, which are disconnected from the cell bodies, degenerate and are replaced by the outgrowth of regenerating axonal sprouts arising from the proximal stump.) This reduction in axonal caliber in the proximal stumps is associated with a selective diminution in the amount of NF protein undergoing slow axonal transport in these axons, with a decrease in axonal NF content, and with reduced conduction velocity. The present report demonstrates that changes in axonal caliber after axotomy correlate with a selective alteration in NF gene expression. Hybridization with specific cDNAs was used to measure levels of mRNA encoding the 68-kDa neurofilament protein (NF68), β-tubulin, and actin in lumbar sensory neurons of rat at various times after crushing the sciatic nerve. Between 4 and 42 days after axotomy by nerve crush, the levels of NF68 mRNA were reduced 2- to 3-fold. At the same times, the levels of tubulin and actin mRNAs were increased several-fold. These findings support the hypothesis that the expression of a single set of neuron-specific genes (encoding NF) directly determines axonal caliber, a feature of neuronal morphology with important consequences for physiology and behavior.

Original languageEnglish (US)
Pages (from-to)3472-3476
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number10
DOIs
StatePublished - 1987
Externally publishedYes

Fingerprint

Axotomy
Intermediate Filaments
Gene Expression
Myelinated Nerve Fibers
Tubulin
Messenger RNA
Axons
Actins
Nerve Crush
Neurofilament Proteins
Neurons
Axonal Transport
Sensory Receptor Cells
Sciatic Nerve
Peripheral Nerves
Nerve Fibers
Complementary DNA
Genes
neurofilament protein NF 68
Cell Body

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Hoffman, P. N., Cleveland, D. W., Griffin, J. W., Landes, P. W., Cowan, N. J., & Price, D. L. (1987). Neurofilament gene expression: A major determinant of axonal caliber. Proceedings of the National Academy of Sciences of the United States of America, 84(10), 3472-3476. https://doi.org/10.1073/pnas.84.10.3472

Neurofilament gene expression : A major determinant of axonal caliber. / Hoffman, P. N.; Cleveland, D. W.; Griffin, J. W.; Landes, P. W.; Cowan, N. J.; Price, D. L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 84, No. 10, 1987, p. 3472-3476.

Research output: Contribution to journalArticle

Hoffman, P. N. ; Cleveland, D. W. ; Griffin, J. W. ; Landes, P. W. ; Cowan, N. J. ; Price, D. L. / Neurofilament gene expression : A major determinant of axonal caliber. In: Proceedings of the National Academy of Sciences of the United States of America. 1987 ; Vol. 84, No. 10. pp. 3472-3476.
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