Jun, Fos, MyoD1, and myogenin proteins are increased in skeletal muscle fiber nuclei after denervation.

After denervation, mRNA levels of the jun and fos protooncogenes and of the muscular differentiation factors myoD1 and myogenin are increased. Here, immunohistochemistry was used (a) to show that this increase in mRNA is followed by an increase in the transcription factor proteins, and (b) to determine which cell populations in skeletal muscle express these factors after denervation. Rat diaphragms were denervated and analyzed after periods of 90 min-8 days. An increase in Fos and Jun as well as MyoD1 and Myogenin immunoreactivity was found after 2-2.5 days of denervation. Fos, MyoD1, and Myogenin immunoreactivity was mostly confined to muscle cell nuclei, whereas Jun antibodies stained muscle cell and some interstitial cell nuclei. A selective expression of any of the four transcription factors in muscle cell nuclei closely associated with motor endplates could not be detected in either denervated or innervated muscle at any time point examined, indicating that synaptic and extrasynaptic muscle cell nuclei are activated simultaneously after denervation. These results suggest that a genetic program which includes protooncogenes and myogenic differentiation factors is activated in skeletal muscle after denervation.