Résumé :
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Satellite cells are muscle progenitor cells that are involved in normal muscle growth and provide a reserve capacity to replace damaged muscle fibers following injury or disease. However, the factors that regulate satellite cell self-renewal, activation and differentiation are not fully defined. In this study we show that homeodomain transcription factor Barx2 is a novel regulator of muscle development and repair. Barx2 is expressed in embryonic myoblasts and adult satellite cells and interacts with other muscle-expressed transcription factors. Barx2 is strongly upregulated in Pax7-expressing satellite cells after muscle injury suggesting a role for Barx2 in satellite cell activation. Consistent with this notion, mice lacking the Barx2 gene show reduced body and muscle mass and defective repair after acute muscle injury, as well as decreased Pax7 expression. In addition, loss of Barx2 in dystrophic mdx mice (Barx2/mdx double null) leads to a much more severe muscle phenotype than either parental strain alone. In satellite cell cultures, Barx2 regulates early events of differentiation and directly controls the expression of muscle-specific genes in cooperation with MyoD and SRF. Moreover, satellite cell cultures prepared from Barx2-/- muscle show a decreased proliferation rate and delayed differentiation together with downregulation of smooth muscle actin and other differentiation markers such as myogenin and myosin heavy chain, suggesting that Barx2 could control differentiation of satellite cells. Moreover, cultured Barx2-/- satellite cells show decreased substrate attachment and migration abilities. Taken together these data suggest that Barx2 is an important factor for satellite cell activation and differentiation.
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