Met receptor signaling in muscle growth and repair

卫星细胞是骨骼肌的干细胞，在出生后和成年机体中有助于肌肉的生长，并参与骨骼肌的修复。因此，有关卫星细胞生物学的知识有助于开发旨在刺激肌肉生长和修复的新疗法。酪氨酸激酶受体Met控制着骨骼肌祖细胞在胚胎中的迁移。Met还指导培养的卫星细胞的激活和增殖，但Met在成年肌肉中的功能尚未被研究。我们建议利用小鼠遗传学来分析Met和Shp2磷酸酶在Met和其他受体下游作用于出生后肌肉生长和修复中的作用。为此，我们将分析携带Cre诱导的Met和Shp2基因突变的小鼠，比较肌肉和肌纤维大小等参数，评估卫星细胞的增殖、维持和分化，并研究骨骼肌的再生潜力。最后，我们将使用在小鼠模型中获得的知识来表征获得性和遗传性肌肉疾病患者的卫星细胞状态。

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.