GATA4 is essential for formation of the proepicardium and regulates cardiogenesis.
The role of GATA4 during the earliest stages of cardiogenesis has not been defined because Gata4 knockout embryos suffer an early developmental arrest caused by deficiencies in extraembryonic visceral endoderm function. We have used tetraploid embryo complementation to rescue these defects and generated clonal embryonic day 9.5 Gata4(-/-) embryos directly from embryonic stem cells. GATA4-null embryos display heart defects characterized by disrupted looping morphogenesis, septation, and a hypoplastic ventricular myocardium. We find that myocardial gene expression is relatively normal in GATA4-null hearts including expression of GATA6. Moreover, GATA4 expression in the endocardium is dispensable for trabeculae formation. Remarkably, the proepicardium is absent in GATA4-null embryos, blocking formation of the epicardium. Therefore, we propose that the observed myocardial defects may be a secondary consequence of loss of the proepicardium. These findings definitively demonstrate a requirement for GATA4 during early cardiac development and identify an essential factor for generation of the proepicardium.
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53202.
Alistair J
AJ
Watt
Michele A
MA
Battle
Jixuan
J
Li
Stephen A
SA
Duncan
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004628:Embryonic Structures / Q000033:anatomy & histology / Q000502:physiology*; D050991:GATA4 Transcription Factor; D005816:Genetic Complementation Test; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology*; D006330:Heart Defects, Congenital; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D010496:Pericardium / Q000033:anatomy & histology / Q000196:embryology*; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D014157:Transcription Factors