Follistatin regulates bone morphogenetic protein-7 (BMP-7) activity to stimulate embryonic muscle growth.

Bone morphogenetic proteins (BMPs) can either promote growth of embryonic muscle by expanding the Pax-3-expressing muscle precursor population or restrict its development by inducing apoptosis. Follistatin, a proposed BMP antagonist, is expressed in embryonic muscle. Deficiency in Follistatin results in muscle defects and postnatal asphyxia. Here, we report that during chick limb development Follistatin enhances BMP-7 action to induce muscle growth but prevents the ability of BMP-7 to induce apoptosis and muscle loss. Follistatin, unlike another BMP-binding protein, Noggin, promotes Pax-3 expression and transiently delays muscle differentiation and thus exerts proliferative signalling during muscle development. We provide data which show that Follistatin binds BMP-7 and BMP-2 at low affinities and that the binding is reversible. These data suggest that Follistatin acts to present BMPs to myogenic cells at a concentration that permits stimulation of embryonic muscle growth.