Transcriptional profiling of myostatin-knockout mice implicates Wnt signaling in postnatal skeletal muscle growth and hypertrophy.

Myostatin is an inhibitor of skeletal muscle growth. Disruption of the Mstn gene in mice results in muscles that weigh two to three times those of controls, but precisely how myostatin signals to exert its effects on muscle is unclear. We used the Affymetrix GeneChip system to identify differences in gene expression between myostatin null and wild-type mice. The results indicated a switch in muscle fiber type, from slow to fast, in the absence of myostatin. They also indicated that myostatin may act upstream of Wnt pathway components. Notably, it repressed expression of Wnt4. Wnt4 was capable of stimulating satellite cell proliferation, while inhibition of Wnt signaling down-regulated satellite cell proliferation. This evidence points to a role for Wnt/calcium signaling in the growth and maintenance of postnatal skeletal muscle. This study offers new insight into potential downstream targets of myostatin, which will be beneficial for elucidation of the mechanism through which myostatin acts to inhibit muscle growth.