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 gener...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 34; pp. 12573 - 12578 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
24.08.2004
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This paper was submitted directly (Track II) to the PNAS office. Abbreviations: En, embryonic day n; ES, embryonic stem; WT1, Wilms' tumor 1; STM, septum transversum mesenchyme. To whom correspondence should be addressed. E-mail: duncans@mcw.edu. Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved July 16, 2004 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0400752101 |