ALTERATION IN MYOSATELLITE CELL COMMITMENT WITH MUSCLE MATURATION

Myosatellite cells are myoblasts found between the basal lamina and sa rcolemma of myofibers of postnatal mice, The extent to which these cel ls are programmed, upon differentiation, to express isoforms of contra ctile protein genes specific to the type of fiber with which they are associated has been evaluated in vitro using myosatellite cells derive d from the soleus and the extensor digitorum longus muscles (EDL) of 4 -day-old and adult transgenic mice, which express nuclear localizing b eta-galactosidase (nls beta-gal) under the control of the promoter and 3' enhancer of the gene encoding fast myosin light chain 3F (MLC3F) ( Kelly et al. [1995] J. Cell Biol, 129:383-396). Cultures were allowed to differentiate either as myocytes (mononucleated cells), to prevent possible modification of the myosatellite phenotype by other myonuclei in mosaic myotubes, or as myotubes, Transgene expression was age rela ted, with 90% and 70% of the myocytes derived from the neonatal EDL an d soleus muscles (muscles that had not yet achieved their mature pheno type), respectively, having nuclei encoding beta-gal; 61% and 32% of t he myocyte nuclei derived from myosatellite cells of the adult EDL (a fast muscle) and the adult soleus muscle (a mixed muscle containing ma ny slow myofibers), respectively, expressed this transgene, Because my osatellite cells found in adult muscles are the progeny of those found in the neonate, an alteration of myosatellite cell commitment to expr ess this transgene occurs with muscle maturation, Because expression o f the transgene in neonatal and adult muscle in vivo reflects the expr ession of the endogenous MLC3F gene (Kelly et al, [1995] J. Cell Biol, 129:383-396), it is likely that expression of the transgene by differ entiated myosatellite cells reflects the extent of commitment of these cells to produce MLC3F, A hypothesis is presented that MLC3F is widel y expressed in developing muscles but eliminated in myofibers that und ergo maturation toward a slower phenotype, (C) 1998 Wiley-Liss, Inc.