Fig. 8. Requirement of MT1-MMP in multiple phases of skeletal muscle tissue development. Myoblast differentiation proceeds through three distinct stages. During elongation, the MMP-dependent ECM remodeling that is critical for the successive fusion step occurs. Time course of MMP-2, MT1-MMP and TIMP-2 expression supports the idea that MMPs are active in the elongation stage. Blocking of MMP activities by inhibitors or specific down-regulation of MT1-MMP by shRNA caused an accumulation of cell-associated fibronectin. Thus, fibronectin may represent ECM components having inhibitory effect for myoblast fusion and have to be cleared by MT1-MMP at this stage. A MT1-MMP deficiency also causes self-destruction of the muscle tissue, which resembles muscular dystrophy. MT1-MMP is responsible for laminin 2 processing in vivo and in vitro, and appears to regulate laminin-based cell adhesion.