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Journal of Neuroscience, Vol 5, 2920-2929, Copyright © 1985 by Society for Neuroscience
Slowing of neurofilament transport and the radial growth of developing nerve fibers
PN Hoffman, JW Griffin, BG Gold and DL Price
Several lines of evidence indicate that neurofilaments are major intrinsic
determinants of axonal caliber in myelinated nerve fibers, and that the
delivery of neurofilaments by slow axonal transport is an important
mechanism by which neurons regulate axonal caliber. To further clarify the
relationship between neurofilament transport and axonal caliber, we
examined transport in developing motor fibers of rat sciatic nerve. In 3-,
10-, 12-, and 20-week-old rats, lumbar motor neurons were labeled by the
intraspinal injection of radioactive amino acids, and the distributions of
labeled cytoskeletal proteins within the sciatic nerve were analyzed at
various times afterwards using sodium dodecyl sulfate-polyacrylamide gel
electrophoresis, gel fluorography, and liquid scintillation spectroscopy.
There was a progressive decline in the velocity of neurofilament transport
with increasing distance along axons undergoing radial growth. By examining
transport in different regions of the nerve in animals of the same age, we
separated age-dependent reductions in velocity from those related to
position along the nerve. The cross-sectional areas of these motor axons
(in the L5 ventral root) increased linearly between 3 and 18 weeks of age.
Quantitative electron microscopic analysis at 3 and 10 weeks of age
revealed that neurofilament density was comparable in fibers of all
calibers, indicating that the radial growth of these myelinated nerve
fibers correlates with a proportional increase in neurofilament content. We
propose that progressive reduction in the velocity of neurofilament
transport along the nerve provides for radial growth during development.
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