BMP signaling regulates satellite cell dependent postnatal muscle growth [RESEARCH ARTICLE]

Amalia Stantzou, Elija Schirwis, Sandra Swist, Sonia Alonso-Martin, Ioanna Polydorou, Faouzi Zarrouki, Etienne Mouisel, Cyriaque Beley, Anaïs Julien, Fabien Le Grand, Luis Garcia, Celine Colnot, Carmen Birchmeier, Thomas Braun, Markus Schuelke, Frederic Relaix, and Helge Amthor

Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here we demonstrate that postnatal satellite cells express components of the Bone Morphogenetic Protein (BMP) signaling machinery. Overexpression of Noggin in postnatal mice, to antagonize BMP ligands, or satellite cell specific knock-out of BMP transmembrane receptor Alk3, or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and up-regulated the expression of cell cycle inhibitors p21 and p57. In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell dependent myofiber growth and the generation of the adult muscle stem cell pool.

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