Modular regulation of cGATA-5 gene expression in the developing heart and gut.

The evolutionarily conserved GATA-5 transcription factor is an early and persistent marker of heart and gut development in diverse vertebrate species. To search for control regions that might regulate the chicken GATA-5 (cGATA-5) gene, we assayed a set of cGATA-5/lacZ constructs in transgenic mice and found evidence for two functionally conserved control regions that regulate different facets of cGATA-5 gene expression. The more distal control region is activated in embryonic endoderm at the head-fold stage, whereas the other control region contains a regulatory module that is activated in a restricted region of endoderm following closure of the gut tube. Remarkably, the latter control region also contains a complex regulatory module that is activated in the cardiac crescent at the head-fold stage and subsequently functions in several mesodermal components of the developing heart, including the outer (epicardial) layer. We discuss these results in terms of possible contributions of epicardial-derived cells to the formation of heart valves, conduction tissue, and compact myocardium. These transgenes thus reveal, and provide a means to further analyze, transcriptional programs for several facets of heart morphogenesis and gut development.