NEUROFILAMENT-DEPENDENT RADIAL GROWTH OF MOTOR AXONS AND AXONAL ORGANIZATION OF NEUROFILAMENTS DOES NOT REQUIRE THE NEUROFILAMENT HEAVY SUBUNIT (NF-H) OR ITS PHOSPHORYLATION

Neurofilaments are essential for establishment and maintenance of axon al 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, heavi ly phosphorylated tail domain of neurofilament heavy subunit (NF-H) is responsible for neurofilament-dependent structuring of axoplasm throu gh intra-axonal crossbridging between adjacent neurofilaments or to ot her axonal structures. To test such a role, homologous recombination w as used to generate NF-H-null mice. In peripheral motor and sensory ax ons, absence of NF-H does not significantly affect the number of neuro filaments or axonal elongation or targeting, but it does affect the ef ficiency of survival of motor and sensory axons. Loss of NF-H caused o nly a slight reduction in nearest neighbor spacing of neurofilaments a nd did not affect neurofilament distribution in either large- of small -diameter motor axons. Since postnatal growth of motor axon caliber co ntinues largely unabated in the absence of NF-H, neither interactions mediated by NF-H nor the extensive phosphorylation of it within myelin ated axonal segments are essential features of this growth.