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Journal of Neuroscience, Vol 12, 4677-4687, Copyright © 1992 by Society for Neuroscience
Neural regulation of N-cadherin gene expression in developing and adult skeletal muscle
CG Hahn and J Covault
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269.
Using monoclonal antibody and cDNA probes, we have studied N-cadherin gene
expression in developing and adult chick skeletal muscle. N- cadherin was
expressed by developing myotubes during the period of initial nerve-muscle
contact but was downregulated within days of innervation. Treatment of
embryos with d-tubocurare partially reversed this downregulation. In the
adult, there were muscle fiber type differences in N-cadherin expression.
N-cadherin was undetectable on normally innervated twitch fibers, while
multiply innervated tonic muscle fibers expressed low but readily
detectable levels of N- cadherin. Denervation led to the renewed expression
of N-cadherin in twitch fibers as well as a marked increase in expression
in tonic fibers. Levels of N-cadherin expressed by tonic fibers could also
be modulated by animal housing conditions that favored either increased or
decreased levels of daily motor activity. Increased motor activity was
correlated with decreased levels of N-cadherin, while decreased motor
activity correlated with increased levels of muscle N-cadherin. Results of
in vitro studies using the calcium channel agonist ryanodine suggest that
changes in intracellular calcium may be the initial signal linking neural
stimulation with changes in muscle fiber expression of N- cadherin.
Together, our results indicate that neural stimulation of chick skeletal
muscle fibers dynamically and reversibly downregulates the expression of
N-cadherin mRNA and protein. This pattern of regulation may be functionally
important in limiting and/or promoting axon growth in innervated versus
denervated muscle and may serve as a molecular model system for studies of
the activity-dependent regulation of gene expression.
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