REQUIREMENT OF THE TRANSCRIPTION FACTOR GATA4 FOR HEART TUBE FORMATION AND VENTRAL MORPHOGENESIS

The zinc finger transcription factor GATA4 has been implicated in hear t development based on its early expression in precardiogenic splanchn ic mesoderm and its ability to activate the expression of a number of cardiac-specific genes. To determine the role of GATA4 in embryogenesi s, we generated mice homozygous for a GATA4 null allele. Homozygous GA TA4 null mice arrested in development between E7.0 and E9.5 because of severe developmental abnormalities. Mutant embryos most notably lacke d a primitive heart tube and foregut and developed partially outside t he yolk sac. In the mutants, the two bilaterally symmetric promyocardi al primordia failed to migrate ventrally but instead remained lateral and generated two independent heart tubes that contained differentiate d cardiomyocytes. We show that these deformities resulted from a gener al loss in lateral to ventral folding throughout the embryo. GATA$ is most highly expressed within the precardiogenic splanchnic mesoderm at the posterior lip of the anterior intestinal portal, corresponding to the region of the embryo that undergoes ventral fusion. We propose th at GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP.