Neurofilament geneexpression: A majordeterminant of axonal caliber (cDNA/mRNA/actin/tubulin)

Within thewidespectrum ofaxonal diame- tersoccurring inmammalian nervefibers, eachclass of neurons hasarelatively restricted range ofaxonal calibers. The control ofcaliber hasfunctional significance because diameter istheprincipal determinant ofconduction velocity inmyelin- ated nerve fibers. Previous observations support thehypothesis thatneurofilaments (NF)aremajor intrinsic determinants of axonal caliber inlarge myelinated nervefibers. Following interruption ofaxons(axotomy) bycrushing orcutting a peripheral nerve, caliber isreduced intheproximal axonal stumps, whichextend fromthecell bodies tothesite of axotomy. (Thedistal axonal stumps, whicharedisconnected fromthecell bodies, degenerate andarereplaced bythe outgrowth ofregenerating axonal sprouts arising fromthe proximal stump.) Thisreduction inaxonal caliber inthe proximal stumps isassociated withaselective diminution inthe amountofNFprotein undergoing slowaxonal transport in these axons, withadecrease inaxonal NFcontent, andwith reduced conduction velocity. Thepresent report demonstrates thatchanges inaxonal caliber after axotomy correlate witha selective alteration inNFgeneexpression. Hybridization with specific cDNAswasusedtomeasure levels ofmRNA encoding the68-kDa neurofilament protein (NF68), ,3-tubulin, andactin inlumbar sensory neurons ofratatvarious times after crushing thesciatic nerve. Between 4and42daysafter axotomy bynerve crush, thelevels ofNF68mRNA werereduced 2-to3-fold. At thesametimes, thelevels oftubulin andactin mRNAswere increased several-fold. Thesefindings support thehypothesis thattheexpression ofa single setofneuron-specific genes (encoding NF)directly determines axonal caliber, afeature of neuronal morphology withimportant consequences forphys- iology andbehavior.