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 Conway, Margaret Buckinghama

Research output: Contribution to journalArticle

208 Citations (Scopus)

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
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

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MicroRNAs
Muscle Cells
Stem Cells
Down-Regulation
Skeletal Muscle
Embryonic Structures
Somites
Muscle Development
3' Untranslated Regions
Transgenes
Cell Movement
Regeneration
Cell Differentiation
Proteins
Maintenance
Muscles
Messenger RNA
Wounds and Injuries

Keywords

  • Onset of mouse myogenesis
  • Satellite cell differentiation

ASJC Scopus subject areas

  • General

Cite this

Muscle stem cell behavior is modified by microRNA-27 regulation of Pax3 expression. / Crist, Colin G.; Montarras, Didier; Pallafacchina, Giorgia; Rocancourt, Didier; Cumano, Ana; Conway, Simon; Buckinghama, Margaret.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 32, 11.08.2009, p. 13383-13387.

Research output: Contribution to journalArticle

Crist, Colin G. ; Montarras, Didier ; Pallafacchina, Giorgia ; Rocancourt, Didier ; Cumano, Ana ; Conway, Simon ; Buckinghama, Margaret. / Muscle stem cell behavior is modified by microRNA-27 regulation of Pax3 expression. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 32. pp. 13383-13387.
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