Myostatin, a negative regulator of muscle growth, functions by
inhibiting myoblast proliferation
M. Thomas, B. Langly, C. Berry, M. Sharma, S. Kirk, J. Bass and
R. Kambadur
Animal Genomics, AgResearch, Private Bag 3123, East Street,
Hamilton, New Zealand
Proceedings of the New Zealand Society of Animal Production.
2000, 60: 85-89
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 C2 C12 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.
Keywords: NZSAPAB;
Myostatin; double muscling; hyperplasia; myoblast; myoblast
proliferation assay; cell cycle.
Last Updated 12-07-2000
