The expression and distribution of tau proteins and messenger RNA in rat dorsal root ganglion neurons during development and regeneration.

Abstract

Microtubule-associated proteins contribute to the balance between stability and plasticity of the neuronal cytoskeleton by modulating assembly and disassembly of microtubules. The tau microtubule-associated proteins exist in several isoforms which are developmentally regulated and differentially distributed. Our objective was to characterize the distribution of tau isoforms in developing and mature dorsal root ganglia neurons and during axonal regeneration following sciatic nerve axotomy. Immunocytochemical analysis was carried out using antibodies that recognize all tau isoforms and a novel antibody that specifically recognizes the high molecular weight isoform. The expression of tau is highly regulated during development. At E14, all dorsal root ganglion neurons express only the low molecular weight tau isoforms. These isoforms are still present in all dorsal root ganglion neurons in neonates, whereas high molecular weight tau isoforms are expressed in a subset of dorsal root ganglion neurons. The switch from low to exclusively high molecular weight tau expression begins at E18 and is completed during the first postnatal week. In the adult, high molecular weight tau is restricted to small- and medium-sized dorsal root ganglion neurons; its distribution largely coincides with the population of substance P and calcitonin gene related peptide peptidergic neurons. This differential distribution was observed in the cell body, dorsal roots and sciatic nerve axons. In contrast to the protein, however, the distribution of high molecular weight tau messenger RNA is not restricted; all dorsal root ganglion neurons express similar tau messenger RNA levels. The discrepancy between the distribution of protein and messenger RNA suggests control at the post-transcriptional or translational levels. Sciatic nerve axotomy which is followed by axonal regeneration did not alter the differential distribution of high molecular weight tau immunostaining. We conclude that the distribution and expression of tau isoforms during axonal regeneration in adult does not recapitulate the developmental pattern.