CONTROL OF MOUSE CARDIAC MORPHOGENESIS AND MYOGENESIS BY TRANSCRIPTION FACTOR MEF2C

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