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Journal of Neuroscience, Vol 9, 1452-1463, Copyright © 1989 by Society for Neuroscience
Rapid induction of the major embryonic alpha-tubulin mRNA, T alpha 1, during nerve regeneration in adult rats
FD Miller, W Tetzlaff, MA Bisby, JW Fawcett and RJ Milner
Division of Preclinical Neurosciences and Endocrinology, Research Institute of Scripps Clinic, La Jolla, California 92037.
The mRNAs for 2 isotypes of alpha-tubulin, termed T alpha 1 and T26, are
differentially regulated in the developing rat nervous system. T alpha 1
alpha-tubulin mRNA is expressed at high levels when neurons extend
processes whereas T26 mRNA is expressed constitutively (Miller et al.,
1987b). We have examined the expression of these 2 alpha- tubulin mRNAs in
regenerating facial and sciatic motor neurons of the rat using Northern
blot and in situ hybridization analyses. T alpha 1 alpha-tubulin mRNA is
rapidly induced in axotomized motor neurons of the facial nerve: increased
levels of mRNA are detectable 4 hr after a lesion is made 1.5 cm distal to
the neuronal cell bodies. T alpha 1 mRNA levels are highest from 3-7 d
postcrush and decline slowly to control levels following functional
reinnervation of facial muscles. In contrast, T26 mRNA levels remain
constant throughout the regeneration process. Total alpha-tubulin mRNA
levels do not change until 1 d postaxotomy; otherwise the changes in
expression are similar to T alpha 1 mRNA, although the relative increase is
not as great. Enhanced T alpha 1 alpha-tubulin mRNA expression also occurs
in motor neurons of crushed or tied sciatic nerve. Ligature or crush of the
sciatic nerve leads to approximately the same peak in the expression of T
alpha 1 mRNA at 7-15 d postaxotomy. Following the facial nerve transection,
under conditions in which reinnervation is prevented, T alpha 1 alpha-
tubulin mRNA levels remain elevated significantly longer than when the
nerve is crushed. Taken together, the data indicate that T alpha 1
alpha-tubulin mRNA is rapidly induced following neuronal axotomy, remains
elevated during the period of axonal regrowth, and is subsequently
down-regulated at the approximate time of target contact. These results are
reminiscent of changes in T alpha 1 mRNA that occur during neuronal
development. This growth-associated pattern of T alpha 1 gene expression
can be modified by inhibiting appropriate regeneration of the damaged
nerve.
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