Induction of T alpha 1 alpha-tubulin mRNA during neuronal regeneration is a function of the amount of axon lost.

Axotomy of mature peripheral neurons leads to upregulation of T alpha 1 alpha-tubulin mRNA. To distinguish whether this increase is due to interruption of target contact or to loss of the axon itself, we developed a model system that allowed us to axotomize mature sympathetic neurons proximal or distal to their cell bodies, severing contact with target tissue in all cases. Sympathetic neurons within the same superior cervical ganglion that project via the internal and external carotid nerves to the eye and to the ear, respectively, were differentially labeled with the retrograde tracers fast blue and fluorogold, and the labeled neurons were then transected close to or far from their cell bodies. In situ hybridization analysis 5 days postaxotomy (the time of peak T alpha 1 mRNA expression) indicated that when eye and ear neurons were both axotomized close to their cell bodies. T alpha 1 mRNA increased to a similar degree in both populations. In contrast, when ear neurons were again cut close, but eye neurons of the same ganglion were transected far from their cell bodies by eye removal, peak T alpha 1 mRNA levels were two- to threefold lower in the eye neurons. Thus, the increase in T alpha 1 mRNA was much lower when only a small amount of axon was lost, even though contact with target tissue was completely interrupted in all groups. These results therefore suggest that neurons normally monitor the status of their axon via a mechanism that allows for graded responses and that the axotomy-induced increase in T alpha 1 mRNA is, to a great extent, due to loss of the nonterminal axon.