Regulation of skeletal muscle sarcomere integrity and postnatal muscle function by Mef2c

Matthew J. Potthoff, Michael A. Arnold, John McAnally, James A. Richardson, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Myocyte enhancer factor 2 (MEF2) transcription factors cooperate with the MyoD family of basic helix-loop-helix (bHLH) transcription factors to drive skeletal muscle development during embryogenesis, but little is known about the potential functions of MEF2 factors in postnatal skeletal muscle. Here we show that skeletal muscle-specific deletion of Mef2c in mice results in disorganized myofibers and perinatal lethality. In contrast, neither Mef2a nor Mef2d is required for normal skeletal muscle development in vivo. Skeletal muscle deficient in Mef2c differentiates and forms normal myofibers during embryogenesis, but myofibers rapidly deteriorate after birth due to disorganized sarcomeres and a loss of integrity of the M line. Microarray analysis of Mef2c null muscles identified several muscle structural genes that depend on MEF2C, including those encoding the M-line-specific proteins myomesin and M protein. We show that MEF2C directly regulates myomesin gene transcription and that loss of Mef2c in skeletal muscle results in improper sarcomere organization. These results reveal a key role for Mef2c in maintenance of sarcomere integrity and postnatal maturation of skeletal muscle.

Original languageEnglish (US)
Pages (from-to)8143-8151
Number of pages9
JournalMolecular and Cellular Biology
Volume27
Issue number23
DOIs
StatePublished - Dec 2007

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Sarcomeres
Skeletal Muscle
Muscles
MEF2 Transcription Factors
Connectin
Muscle Development
Embryonic Development
Basic Helix-Loop-Helix Transcription Factors
Microarray Analysis
Genes
Proteins
Transcription Factors
Maintenance
Parturition

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Regulation of skeletal muscle sarcomere integrity and postnatal muscle function by Mef2c. / Potthoff, Matthew J.; Arnold, Michael A.; McAnally, John; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.

In: Molecular and Cellular Biology, Vol. 27, No. 23, 12.2007, p. 8143-8151.

Research output: Contribution to journalArticle

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