This proposal is concerned with two members of the TGF-b superfamily isolated by the investigator, GDF-8 and GDF-11. GDF-8 is expressed almost exclusively in developing and adult skeletal muscle and null mutant mice show a massive and widespread increase in skeletal muscle growth. There are six aims to investigate the biological functions of GDF-8 and GDF-11. The first aim is to characterize the expression patterns at the RNA and protein level of GDF-8 and GDF-11. This has already been achieved for GDF-8 transcripts. The second aim is to characterize the phenotypes of the GDF-8 and GDF-11 null mice. The third specific aim is to purify the proteins from mammalian cells and determine the interaction between the various processed forms. The fourth aim is to determine the distribution of the GDF-8 and GDF-11 receptors. The fifth aim is to test the function of GDF-8 and GDF-11 protein on cultured cells to test the hypothesis that GDF-8 acts as an inhibitor of myoblast proliferation. The final aim is to clone the genes for the GDF-8 and GDF-11 receptors.