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First published online 26 September 2006
doi: 10.1242/jcs.03186

This Article Figures Only Full Text Full Text (PDF) An erratum has been published All Versions of this Article: jcs.03186v1 119/20/4315    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Karamboulas, C. Articles by Skerjanc, I. S. Search for Related Content PubMed PubMed Citation Articles by Karamboulas, C. Articles by Skerjanc, I. S.

Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis

¹ Department of Biochemistry, Medical Sciences Building, University of Western Ontario, London, Ontario, N6A 5C1, Canada
² Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada
³ Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada
⁴ Division of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center ML7020, Cincinnati, OH, USA

^* Author for correspondence (e-mail: iskerjan{at}uottawa.ca)

Accepted 25 July 2006

Myocyte enhancer factors (MEF2s) bind to muscle-specific promoters and activate transcription. Drosophila Mef2 is essential for Drosophila heart development, however, neither MEF2C nor MEF2B are essential for the early stages of murine cardiomyogenesis. Although Mef2c-null mice were defective in the later stages of heart morphogenesis, differentiation of cardiomyocytes still occurred. Since there are four isoforms of MEF2 factors (MEF2A, MEF2B, MEF2C and MEF2D), the ability of cells to differentiate may have been confounded by genetic redundancy. To eliminate this variable, the effect of a dominant-negative MEF2 mutant (MEF2C/EnR) during cardiomyogenesis was examined in transgenic mice and P19 cells. Targeting the expression of MEF2C/EnR to cardiomyoblasts using an Nkx2-5 enhancer in the P19 system resulted in the loss of both cardiomyocyte development and the expression of GATA4, BMP4, Nkx2-5 and MEF2C. In transiently transgenic mice, MEF2C/EnR expression resulted in embryos that lacked heart structures and exhibited defective differentiation. Our results show that MEF2C, or genes containing MEF2 DNA-binding sites, is required for the efficient differentiation of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of MEF2 from Drosophila to mammals.

Key words: Cardiomyogenesis, MEF2C, Transgenic mice

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