Myogenic activity of the dominant-negative form of type II receptor for myostatin during skeletal muscle development *
Myostatin（MSTN）is transiently expressed in developing skeletal muscle, and negatively regulates muscle growth, in that a loss of function mutation of the MSTN gene results in excess muscle formation. MSTN is known to act through initial binding of mature peptide to the type II receptor, activin receptor IIA and IIB（ActRIIA and ActRIIB）, after proteolytic cleavage at the junction between N-terminal propeptide and C-terminal mature peptide. Whereas ActRIIB is expressed predominantly in the developing neural tube, ActRIIA is expressed in the myogenic precursor cells derived from the dermomyotome. Overexpression of the extracellular domain of ActRIIA and ActRIIB effectively blocks MSTN signaling through inhibition of the receptor binding of MSTN. The extracellular domain of ActRII produced in a conditioned medium of DF-1 cells caused an increase in myogenic differentiation of the C2C12 myoblast cell line and of a primary culture of chick embryo mesenchymal cells. Dominant-negative forms of ActRIIA and ActRIIB both effectively stimulate myogenic differentiation. (Accepted on June 13，2006)
