Neuregulin stimulates myogenic differentiation in an autocrine manner

During myogenesis, mononucleated myoblasts form multinucleated myotubes by membrane fusion. Efficiency of this intercellular process can be maximized by a simultaneous progress, with a time window, of other neighboring myobla sts in the differentiation program. This phenomenon has been described as t he community effect. It proposes the existence of a molecule that acts as a differentiation-inducing signal to a group of identical cells. Here,we sho w that neuregulin is a strong candidate for this molecule in myoblast diffe rentiation. The expression of neuregulin increased rapidly but transiently at early stage of differentiation of rat L6 cells. Neuregulin showed a pote nt differentiation-promoting activity in membrane fusion and expression of myosin heavy chain. The antibodies raised against neuregulin and its cognat e receptor ErbB3, which were capable of neutralizing the signal pathway, in hibited myotube formation and expression of myosin heavy chain in both L6 c ells and primary rat myoblasts. The progress of differentiation was mostly halted after the expression of myogenin and cell cycle arrest. These result s suggest that the activation of an autocrine signaling of neuregulin may p rovide a basic mechanism for the community effect observed in the different iation of the embryonic muscle cells.