Nerve-dependent and -independent patterns of mRNA expression in regenerating skeletal muscle

Muscle regeneration was used to assess the roles of innervation and intrinsic genetic information in the acquisition of predominant slow and fast contractile protein mRNA profiles in adult skeletal muscle. Rat soleus (slow) and EDL (fast) muscles were allowed to regenerate in the presence and absence of their respective slow and fast nerves. Levels of mRNAs encoding fast, slow, and cardiac contractile protein isoforms were quantitatively determined at specific times during regeneration. All muscles initially expressed a heterogeneous pattern of fast, slow, and cardiac isoform mRNAs during myotube formation. Subsequently, the EDL muscle made a transition to a predominantly fast profile of mRNAs which was independent of innervation. The mRNA profile for the noninnervated regenerating soleus muscle was similar to both the innervated and the noninnervated EDL muscle profile. Thus, the decision to express predominantly fast isoform mRNAs is intrinsic to in vivo muscle regeneration with the fast nerve not appearing to be informative. In contrast, acquisition of a slow mRNA profile is dependent on the presence of a slow nerve. The mRNAs encoding slow isoforms from all of the contractile protein gene families are upregulated during the period of reestablishment of neuromuscular transmission. Additionally, there is no concomitant down-regulation of the fast isoform mRNAs upon reinnervation in the soleus regenerate. We propose that information both intrinsic to the muscle and supplied by the in vivo environment acts to provide potential isoform mRNA options to the regenerating muscle.