Postnatal increases in neurofilament gene expression correlate with the radial growth of axons

Abstract

Neurofilament gene expression appears to play an important role in regulating axonal calibre. In the dorsal root ganglia of mature mammals, large sensory neurons contain high levels of neurofilament mRNAs and give rise to large-calibre myelinated axons (with diameters up to 8 μm in rat), while small sensory neurons contain undetectable levels of neurofilament mRNAs and give rise to unmyelinated axons (with diameters less than 1 μm). In the present study we used a combination of morphological and molecular approaches to examine the relationships among postnatal increases in neurofilament gene expression, growth in perikaryal size, growth in axonal calibre and myelin formation in lumbar sensory neurons of rat. Usingin situ hybridization, three populations of sensory neurons could be clearly distinguised at birth: (1) neurons containing relatively high levels of neurofilament mRNAs; (2) neurons containing low levels of neurofilament mRNAs; and (3) neurons containing undetectable levels of neurofilament mRNAs. Perikaryal size was greater for neurons with high levels of neurofilament mRNAs than for those with either low or undetectable levels. The proportion of neurons expressing high levels of neurofilament mRNAs increased from approximately 10% at birth to 30% by 28 days of age; increases in the abundance of neurofilament mRNAs in these neurons between 0 and 28 days of age, as documented by blot analyses of RNA purified from dorsal root ganglia, correlated with increases in perikaryal size. This postnatal rise in neurofilament gene expression also correlated with an increase in the cross-sectional areas of myelinated axons in the L5 dorsal root. As axons matured in their relationship to Schwann cells (polyaxonal pockets → ensheathed → segregated → myelinated), their cross-sectional areas increased. Thus, growth in both perikaryal size and axonal calibre correlated closely with increased neurofilament gene expression in these sensory neurons. These findings are consistent with the hypothesis that neurofilament expression plays an important role in the sequence of events leading to the radial growth and myelination of axons.