© The Rockefeller University Press,
0021-9525/1998//171 $5.00
The Journal of Cell Biology, Volume 143, Number 1,
, 1998 171-181
Neurofilament-dependent Radial Growth of Motor Axons and Axonal Organization of Neurofilaments Does Not Require the Neurofilament Heavy Subunit (NF-H) or Its Phosphorylation
Mala V. Rao*,
Megan K. Houseweart*,
,
Toni L. Williamson*,
Thomas O. Crawford||,
Janet Folmer¶, and
Don W. Cleveland*,
,
* Ludwig Institute for Cancer Research,
Division of Cellular and Molecular Medicine,
Department of Neuroscience, University of California at San Diego, La Jolla, California 92093; and || Department of Neurology, School of Medicine, ¶ School of Hygiene, Johns Hopkins Medical Institutes, Baltimore, Maryland 21205
Neurofilaments are essential for establishment and maintenance of axonal diameter of large myelinated axons, a property that determines the velocity of electrical signal conduction. One prominent model for how neurofilaments specify axonal growth is that the 660–amino acid, heavily phosphorylated tail domain of neurofilament heavy subunit (NF-H) is responsible for neurofilament-dependent structuring of axoplasm through intra-axonal crossbridging between adjacent neurofilaments or to other axonal structures. To test such a role, homologous recombination was used to generate NF-H–null mice. In peripheral motor and sensory axons, absence of NF-H does not significantly affect the number of neurofilaments or axonal elongation or targeting, but it does affect the efficiency of survival of motor and sensory axons. Loss of NF-H caused only a slight reduction in nearest neighbor spacing of neurofilaments and did not affect neurofilament distribution in either large- or small-diameter motor axons. Since postnatal growth of motor axon caliber continues largely unabated in the absence of NF-H, neither interactions mediated by NF-H nor the extensive phosphorylation of it within myelinated axonal segments are essential features of this growth.
Key Words: neurofilaments radial growth axoplasm motor neurons sensory neurons
Abbreviations used in this paper: ES, embryonic stem; NF-H, NF-M, and NF-L, heavy, mid-sized, and light neurofilament subunits.

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