The Regulation of Myosin-Light-Chain Synthesis in Heterokaryons between Differentiated and Undifferentiated Myogenic Cells

Embryonic myoblasts from a variety of species are able to undergo a process of terminal differentiation in vitro. Freshly isolated myoblasts are morphologically and biochemically undifferentiated. After dividing several times, they become postmitotic, spontaneously fuse to form multinucleated myotubes, and initiate the synthesis of a variety of muscle-specific proteins. The synthesis of these proteins is coordinately controlled (Devlin and Emerson, 1978; Garrels, 1979), and although some translational regulation may be involved (Buckingham et al., 1976; Bag and Sarkar, 1976), the major control appears to be primarily transcriptional (John et al., 1977; Strohman et al., 1977; Perriard, 1979). Little is known concerning the mechanisms by which the myoblasts shift from a program of cell division to one of terminal differentiation. In the study reported herein, polyethylene-glycol-induced fusion products (heterokaryons) between terminally differentiated skeletal myocytes and undifferentiated myoblasts were used to determine whether the formation of muscle-specific protein is under positive or negative control. Our results suggest that the synthesis of myosin is under positive inductive regulation, since undifferentiated rat myoblasts were observed to synthesize rat skeletal-myosin light chains when fused to differentiated chick myocytes.