GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc Natl Acad Sci U S A 2004 Aug 24;101(34):12573-8
Date
08/18/2004Pubmed ID
15310850Pubmed Central ID
PMC515098DOI
10.1073/pnas.0400752101Scopus ID
2-s2.0-4344565788 (requires institutional sign-in at Scopus site) 302 CitationsAbstract
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.
Author List
Watt AJ, Battle MA, Li J, Duncan SAMESH terms used to index this publication - Major topics in bold
AnimalsDNA-Binding Proteins
Embryo, Mammalian
Embryonic Structures
GATA4 Transcription Factor
Genetic Complementation Test
Heart
Heart Defects, Congenital
Mice
Mice, Knockout
Morphogenesis
Myocardium
Pericardium
Stem Cells
Transcription Factors
