Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis.

TLDR

GATA4 is a zinc‑finger transcription factor expressed early in precardiogenic splanchnic mesoderm, where it activates cardiac genes and is highly enriched at the posterior lip of the anterior intestinal portal, the site of ventral fusion. The authors generated GATA4 null mice to test whether GATA4 is required for migration or folding of precardiogenic mesoderm during embryogenesis. They created homozygous GATA4 knockout embryos and examined their development, focusing on mesodermal migration and folding at the anterior intestinal portal. GATA4 null embryos arrest between E7.0–E9.5, lack a primitive heart tube and foregut, develop partially outside the yolk sac, and exhibit two lateral heart tubes due to a global loss of lateral‑to‑ventral folding.

Abstract

The zinc finger transcription factor GATA4 has been implicated in heart development based on its early expression in precardiogenic splanchnic mesoderm and its ability to activate the expression of a number of cardiac-specific genes. To determine the role of GATA4 in embryogenesis, we generated mice homozygous for a GATA4 null allele. Homozygous GATA4 null mice arrested in development between E7.0 and E9.5 because of severe developmental abnormalities. Mutant embryos most notably lacked a primitive heart tube and foregut and developed partially outside the yolk sac. In the mutants, the two bilaterally symmetric promyocardial primordia failed to migrate ventrally but instead remained lateral and generated two independent heart tubes that contained differentiated cardiomyocytes. We show that these deformities resulted from a general loss in lateral to ventral folding throughout the embryo. GATA4 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 that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP.