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Publication : GATA4 is essential for formation of the proepicardium and regulates cardiogenesis.

First Author  Watt AJ Year  2004
Journal  Proc Natl Acad Sci U S A Volume  101
Issue  34 Pages  12573-8
PubMed ID  15310850 Mgi Jnum  J:92434
Mgi Id  MGI:3052615 Doi  10.1073/pnas.0400752101
Citation  Watt AJ, et al. (2004) GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc Natl Acad Sci U S A 101(34):12573-8
abstractText  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.
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