Neural and hormonal control of expression of myogenic regulatory factor genes during regeneration of Xenopus fast muscles: myogenin and MRF4 mRNA accumulation are neurally regulated oppositely.

With the aim to investigate the influence of both innervation and thyroid hormone, on the expression of the MRFs during muscle regeneration, we performed cardiotoxin injury-induced regeneration experiments on fast muscles of adult Xenopus laevis subjected to different experimental conditions, including denervation and T3 treatment, and analyzed the accumulation of the four myogenic regulatory factors (MRFs) using RT-PCR and in situ hybridization. We show here that manipulation of hormone levels or innervation resulted in differential alterations of MRF expression. Denervation and T3 treatment transiently down-regulated Myf-5 mRNA levels at the beginning of the regeneration process. Myf-5 was the only myogenic factor subject to thyroid hormone influence. Muscle denervation persistently reduces the levels of MRF4 transcripts as early as the first stages of regeneration, whereas the levels of myogenin mRNA were increased in the late stages of regeneration. This suggests that MRF4 expression may be induced by innervation and hence may be involved in mediating transcriptional responses to innervation and that myogenin expression may compensate for the down-regulation of MRF4 gene. This switch in MRF gene expression following denervation could have important consequences for the ability of Xenopus regenerating muscles to recover function after denervation.