DEVELOPMENTAL SHIFT OF MYOSIN HEAVY-CHAIN MESSENGER-RNA EXPRESSION DUE TO NEURAL FACTOR(S) AND MUSCLE-ACTIVITY

The adult ventricular isoform of chicken myosin heavy chain (MHC-V) is transiently expressed in all skeletal muscle primordia analyzed and i s completely repressed around embryonic days 10-12, when functional in nervation is established. By ribonuclease protection assay, we demonst rated that denervation of the adult anterior latissimus dorsi muscle r esulted in reexpression of MHC-V mRNA. In contrast, treatment of prima ry cultures of fetal breast or leg muscles with embryonic brain extrac t or conditioned media from glial or neuroblastoma cell lines, but not from a myogenic cell line or primary muscle cell cultures, led to inh ibition of MHC-V expression. This inhibitory activity was abolished by heating and increased with protein concentration. The acquisition of both brain inhibitory activity and the competence of myogenic cells to downregulate MHC-V mRNA expression were age dependent. Furthermore, e ither paralysis of muscle in ovo by curare or contraction arrest of cu ltured myotubes resulted in persistent expression of MHC-V mRNA. Thus a putative soluble factor(s) of nerve origin as well as muscle activit y are involved in the developmental downregulation of MHC-V expression in muscle primordia.