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Muscle stem cell behavior is modified by microRNA-27 regulation of Pax3 expression.

Abstract : Skeletal muscle stem cells are regulated by Pax3/7. During development, Pax3 is required for the maintenance of these cells in the somite and their migration to sites of myogenesis; high levels of Pax3 interfere with muscle cell differentiation, both in the embryo and in the adult. Quantitative fine-tuning of Pax3 is critical, and microRNAs provide a potential mechanism. We identify microRNA-27b (miR-27b), which directly targets the 3'-UTR of Pax3 mRNA, as such a regulator. miR-27b is expressed in the differentiating skeletal muscle of the embryonic myotome and in activated satellite cells of adult muscle. In vivo overexpression of a miR-27b transgene in Pax3-positive cells in the embryo leads to down-regulation of Pax3, resulting in interference with progenitor cell migration and in premature differentiation. In a complementary experiment, miR-27b inhibitors were transfected into cultures of adult muscle satellite cells that normally express miR-27b at the onset of differentiation, when Pax3 protein levels undergo rapid down-regulation. Interference with miR-27b function results in continuing Pax3 expression leading to more proliferation and a delay in the onset of differentiation. Pax7 levels are not affected. Introduction of miR-27b antagomirs at a site of muscle injury in vivo also affects Pax3 expression and regeneration in vivo. We therefore conclude that miR-27b regulates Pax3 protein levels and this down-regulation ensures rapid and robust entry into the myogenic differentiation program.
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Contributor : Marie-Christine Vougny Connect in order to contact the contributor
Submitted on : Friday, October 30, 2009 - 2:48:01 PM
Last modification on : Tuesday, May 31, 2022 - 10:20:13 AM

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Colin G. Crist, Didier Montarras, Giorgia Pallafacchina, Didier Rocancourt, Ana Cumano, et al.. Muscle stem cell behavior is modified by microRNA-27 regulation of Pax3 expression.. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 (32), pp.13383-7. ⟨10.1073/pnas.0900210106⟩. ⟨pasteur-00429032⟩



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