Abstract

Myostatin, a member of the transforming growth factor-b (TGF-b) superfamily has been shown to be a negative regulator of myogenesis. However, the molecular mechanism of myostatin function is, so far, not understood. Here we show that myostatin is synthesised and proteolytically processed in myoblasts and that myostatin functions by controlling the proliferation of muscle precursor cells. When actively growing C2C12 myoblasts were incubated with myostatin, the proliferation of myoblasts decreased with increasing levels of myostatin. Furthermore, we show that the myoblast inhibition by myostatin is reversible, such that, myoblasts retain the ability to proliferate after myostatin protein is removed. FACS analysis revealed that myostatin inhibited myoblast proliferation through preventing the progression of myoblasts from the G1 to S-phase of the cell cycle. Thus, we propose that the generalised muscular hyperplasia phenotype observed in animals that lack functional myostatin could be as a result of deregulated myoblast proliferation.

M, Thomas, B Langly, C Berry, M Sharma, S Kirk, J Bass, and R Kambadur

Proceedings of the New Zealand Society of Animal Production, Volume 60, Hamilton, 85-89, 2000