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

Colin G. Crist, Didier Montarras, Giorgia Pallafacchina, Didier Rocancourt, Ana Cumano, Simon J. Conway, Margaret Buckinghama

Research output: Contribution to journalArticle

226 Scopus citations

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 downregulation ensures rapid and robust entry into the myogenic differentiation program.

Original languageEnglish (US)
Pages (from-to)13383-13387
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number32
DOIs
StatePublished - Aug 11 2009

Keywords

  • Onset of mouse myogenesis
  • Satellite cell differentiation

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Muscle stem cell behavior is modified by microRNA-27 regulation of Pax3 expression'. Together they form a unique fingerprint.

  • Cite this