The role of neurofilament transport in the radial growth of myelinated axons

The cross-sectional area of myelinated axons increases greatly during postnatal development in mammals and is an important influence on axonal conduction velocity. This radial growth is driven primarily by an accumulation of neurofilaments, which are cytoskeletal polymers that serve a space-filling function in axons. Neurofilaments are assembled in the neuronal cell body and transported into axons along microtubule tracks. The maturation of myelinated axons is accompanied by an increase in neurofilament gene expression and a decrease in neurofilament transport velocity, but the relative contributions of these processes to the radial growth are not known. Here, we address this question by computational modeling of the radial growth of myelinated motor axons during postnatal development in rats. We show that a single model can explain the radial growth of these axons in a manner consistent with published data on axon caliber, neurofilament and microtubule densities, and neurofilament transport kinetics in vivo. We find that the increase in the cross-sectional area of these axons is driven primarily by an increase in the influx of neurofilaments at early times and by a slowing of neurofilament transport at later times. We show that the slowing can be explained by a decline in the microtubule density.