Met receptor signaling in muscle growth and repair

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Satellite cells, the stem cells of skeletal muscle, contribute to muscle growth in the postnatal and the adult organism, and participate in skeletal muscle repair. Knowledge about satellite cell biology can thus contribute towards the development of novel therapies that aim to stimulate muscle growth and repair. The tyrosine kinase receptor Met controls migration of skeletal muscle progenitor cells in the embryo. Met also directs the activation and proliferation of cultured satellite cells, but Met functions in the adult muscle have not been studied. We propose to analyze the role of Met, and of the Shp2 phosphatase that acts downstream of Met and other receptors, in postnatal muscle growth and repair using mouse genetics. For this, we will analyze mice that carry cre-induced mutations in the Met and Shp2 genes, and compare parameters such as muscle and myofiber size, assess proliferation, maintenance and differentiation of satellite cells, and investigate the regeneration potential of the skeletal muscle. Finally, we will use the knowledge gained in the murine model to characterize the status of satellite cells in patients with acquired and inherited muscle disease.