We have isolated and characterized Xenopus cDNA clones for a new transcription factor that represents an early marker for the developing heart. The cDNAs encode a protein that we have designated GATA-4; it contains the highly conserved DNA-binding domain that characterizes this family of cell-type restricted transcriptional activators. Whole-embryo in situ analysis of Xenopus embryos demonstrates that the GATA-4 gene is transcribed in presumptive cardiac ventral mesoderm at the time that bilateral progenitors fuse and form the cardiac tube. GATA-4 is therefore the earliest molecular marker of cardiogenesis yet characterized. By stage 30, the GATA-4 mRNA is expressed in the developing atria and ventricles; at stage 38, cross-sections reveal that the gene is active in the endocardial layer, but not in myocardium. By stage 40, GATA-4 message is detected in the great vessels. In the adult frog, the GATA-4 gene is highly transcribed in heart and gut; lower levels of message are detected in various endoderm-derived tissues and gonads. Expression in the stomach is largely confined to the epithelium. The GATA-4 gene is first activated at stage 11; mRNA is initially present throughout the marginal zone of explants and later partially localized to the ventral marginal zone. GATA-4 mRNA is also detected at high levels in cultured endodermal explants derived from the vegetal region of early embryos. In mesoderm induction experiments, GATA-4 transcription is not induced in animal caps treated with activin or bFGF. The GATA-4 gene may provide a new early marker for studying the inductive processes that lead to the formation of the cardiovascular system and for the specification of the endocardial lineage.
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