The Relative Contributions of Neurofilament Gene Expression and Neurofilament Transport in Axonal Caliber Growth

During the postnatal stage of mammalian development, the myelinated axon expands radially until it reaches a target caliber that influences axonal conduction velocity and in turn neuronal function. Hence, the growth of axon caliber is an important developmental process to understand. This radial growth is mainly driven by an accumulation of neurofilaments (NFs), which are cytoskeletal polymers known for their space-filling role in axons. They are assembled in the neuronal cell body and transported into the axon along microtubules (MTs). The growth of axonal caliber is accompanied by an increase in NF gene expression and a decrease in NF transport velocity along the axon, but the relative contributions of these processes to the growth are not known. Guided by published data on axonal area, NF and MT densities as well as NF transport kinetics in vivo, we address this question by computational modeling of the growth of myelinated motor axons in rats. We find that the radial growth of these axons is mainly driven by an increase in NF influx at the earlier stages of development and by the slowing of NF transport at later times. We conclude that a decline in MT density provides a mechanism for the observed slowing.