Control of Mouse Cardiac Morphogenesis and Myogenesis by Transcription Factor MEF2C

TLDR

Members of the myocyte enhancer factor–2 (MEF2) family of MADS‑box transcription factors bind an A‑T–rich DNA sequence associated with muscle‑specific genes, and the murine MEF2C gene is expressed in heart precursor cells before formation of the linear heart tube. In MEF2C‑null mice, heart tube looping fails, the right ventricle does not form, and key cardiac muscle genes, including dHAND, are down‑regulated, demonstrating that MEF2C is essential for cardiac myogenesis and right ventricular development.

Abstract

Members of the myocyte enhancer factor–2 (MEF2) family of MADS (MCM1, agamous, deficiens, serum response factor)–box transcription factors bind an A-T–rich DNA sequence associated with muscle-specific genes. The murine MEF2C gene is expressed in heart precursor cells before formation of the linear heart tube. In mice homozygous for a null mutation of MEF2C , the heart tube did not undergo looping morphogenesis, the future right ventricle did not form, and a subset of cardiac muscle genes was not expressed. The absence of the right ventricular region of the mutant heart correlated with down-regulation of the dHAND gene, which encodes a basic helix-loop-helix transcription factor required for cardiac morphogenesis. Thus, MEF2C is an essential regulator of cardiac myogenesis and right ventricular development.