A Slowing of Neurofilament Transport and an Increase in Neurofilament Influx Both Contribute to the Radial Growth of Axons During Development

Neurofilaments (NFs) are abundant space-filling cytoskeletal protein polymers in axons. They are assembled in the nerve cell body and transported towards the nerve terminal along microtubule tracks at an average velocity of 0.1 to 1mm/day. During postnatal development, NFs accumulate in axons causing them to expand radially. In this way, NFs determine one of the basic cable properties of axons that influences axonal conduction velocity. Theoretically, this NF accumulation can occur by an increased expression and influx of NFs from the cell body and/or by a slowing of NF transport in the axon. To explore the relative contribution of these two mechanisms, we developed a computational model that simulates NF transport and axon growth. We compared the model to published experimental data on the kinetics of NF transport obtained by radio-isotopic pulse-labeling and published experimental data relating axon caliber to NF and microtubule content during axonal growth. We constrained the model to match the increase in axon caliber and the speed and shape of the distribution of radiolabeled NFs as they traverse the axon during maturation of axons in rat sciatic nerve. We found that slowing alone is not sufficient to explain the observed NF accumulation and that both a slowing of NF transport and an increase in NF influx from the cell body contribute to the expansion of axons during postnatal development.