Following muscle injury, quiescent muscle stem cells (satellite cells) are activated and then proliferate and differentiate to regenerate myofibres. Wnt signalling regulates the differentiation of activated satellite cells, but what other factors control skeletal muscle regeneration? On , Francisco Naya and co-workers report that the transcription factor myocyte enhancer factor 2A (MEF2A) plays an essential role in skeletal muscle regeneration in adult mice. Myofibre formation is impaired in injured Mef2a knockout mice, the researchers report, and this impaired injury response is associated with downregulation of the Gtl2-Dio3 locus, the largest known mammalian microRNA (miRNA) cluster. Notably, a subset of the miRNAs in this locus represses secreted Frizzled-related proteins (sFRPs), which are inhibitors of Wnt signalling. Consistent with these data, sFRP expression is upregulated and Wnt activity is attenuated in injured Mef2a knockout muscle. These and other results suggest that miRNA-mediated modulation of Wnt signalling by MEF2A is required for muscle regeneration and suggest that targeting this pathway might enhance the regeneration of diseased muscle.
