GATA4 is essential for formation of the proepicardium and regulates cardiogenesis

We find that myocardial gene expression is relatively normal in GATA4-null hearts including expression of GATA6

A. J. Watt; M. A. Battle; J. Li; S. A. Duncan

2004

Scholarcy highlights

  • 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
  • In agreement with previous studies, Gata4Ϫ/Ϫ embryonic stem cells were unable to differentiate into visceral endoderm in vitro confirming that they are functionally null for GATA4
  • As has been shown, Gata4Ϫ/Ϫ embryos complemented with wild-type visceral endoderm survive to E9.5, rescuing the developmental defects, including cardia bifida, associated with conventionally produced Gata4 knockout embryos
  • Southern blot analyses demonstrated that these embryos were genetically identical to the Gata4Ϫ/Ϫ ES cells, and immunostaining experiments confirmed that they contained no functional GATA4 protein
  • It is worth noting that embryos harboring a mutation affecting the interaction of GATA4 with friend-of-GATA 2 survived until E12.5
  • These data are supported by defects in the proepicardium derived coronary vasculature of E12.5 embryos with a point mutation in GATA4. At this time, rule out a cell-autonomous requirement for GATA4 in the myocardium, we propose that the absence of the septum transversum mesenchyme and the proepicardium is a primary cause of the cardiac phenotype associated with loss of GATA4
  • Reduced trabeculation, enhanced cardiomyocyte differentiation, and defective outflow tract separation, as seen in Gata4Ϫ/Ϫ embryos, are features of Retinoic acid deficiency and inactivation of genes in the RA signaling pathway

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