GATA4 and GATA5 are essential for heart and liver development in Xenopus embryos

In this study we show that in Xenopus embryos GATA5 is essential for early development of heart and liver precursors. In addition, we have found that in Xenopus embryos GATA4 is important for development of heart and liver primordia following their specification, and that in this role it might interact with GATA6.Our results suggest that GATA5 acts earlier than GATA4 to regulate development of heart and liver precursors, and indicate that one early direct target of GATA5 is homeobox gene Hex.GATA4/5/6 Zinc finger-containing transcription factors are regulators of gene expression in multiple tissues derived from mesoderm and endoderm in vertebrate embryos and adults [1-4]. They are expressed in overlapping patterns and share domain structure and most of their biochemical activities, including DNA binding site preference, raising a possibility of redundant function in vivo. Genetic analyses of the roles of GATA4/5/6 genes in vertebrate development has so far implicated that individual factors have unique and shared roles. In the mouse GATA4 initially plays an essential role in endodermal development and indirectly in early heart morphogenesis [5-7]. Later roles of GATA4 have been revealed by analysis of a non-null allele that blocks interaction with FOG2 cofactor, by myocardial-specific null mutation, and by careful analysis of heterozygous null mice [8-10]. A role for GATA4 in the mouse liver development was recently examined by tetraploid embryo complementation, and this work has indicated that GATA4 is required for expansion of liver bud [11]. In zebrafish, knockdown of GATA4 by specific morpholino oligonucleotides (MO) has been shown to affect development of heart and liver precursors after their specification, in broad agreement with the results obtained in the mouse model [12].GATA6 is indispensable for development of exrtraembryonic endoderm in the mouse, and also has later roles in the developing liver and heart, following their specification [13]. These findi