DIFFERENTIAL EXPRESSION OF MUSCLE REGULATORY FACTOR GENES IN NORMAL AND DENERVATED ADULT-RAT HINDLIMB MUSCLES

Skeletal muscle represents an excellent model system in which to exami ne regulatory mechanisms that modulate gene expression in the mature a dult organism. Individual muscle fibers can be categorized as fast- or slow-twitch based upon several physiological and molecular criteria, including metabolic enzyme activity and contractile protein isoforms. Each property can be influenced by a variety of factors such as change s in motor neuron activity or alterations in hormone levels, although the molecular pathways by which environmental factors affect gene expr ession remain largely unknown. As a first step in identifying potentia l regulators of fiber-type diversity, the expression patterns of four basic/helix-loop-helix muscle regulatory factors (MRFs), referred to a s MyoD, myogenin, Myf-5, and MRF4, were examined in normal adult rat m uscles which differed in their phenotypic properties. As expected, all four MRFs were expressed at detectable levels in the muscles studied. However, different muscles accumulated different proportions and comb inations of MRF transcripts. For example, myogenin expression was maxi mally detected in slow-twitch muscles whereas MyoD transcripts were fo und predominantly in muscles exhibiting a fast-twitch phenotype. Induc ed phenotypic changes in two fast-twitch muscles via denervation lead to a large and rapid increase in transcript levels of all four MRFs as early as 24 hr following denervation, with myogenin transcripts appro aching 150-200-fold higher levels than innervated contralateral muscle s within 7 days. These results suggest that; myogenin, as well as the other three MRFs, may be involved in both the initial establishment as well as maintenance of fiber-type diversity in the developing organis m. (C) 1993 Wiley-Liss, Inc.