GATA-4:FOG interactions regulate gastric epithelial development in the mouse.

Transcription factor GATA-4 is a key participant in cytodifferentiation of the mouse hindstomach. Here we show that GATA-4 cooperates with a Friend-of-GATA (FOG) cofactor to direct gene expression in this segment of gut. Immunohistochemical staining revealed that GATA-4 and FOG-1 are co-expressed in hindstomach epithelial cells from embryonic days (E) 11.5 to 18.5. The other member of the mammalian FOG family, FOG-2, was not detected in gastric epithelium. To show that GATA-4:FOG interactions influence stomach development, we analyzed Gata4(ki/ki) mice, which express a mutant GATA-4 that cannot bind FOG cofactors. Sonic Hedgehog, an endoderm-derived signaling molecule normally down-regulated in the distal stomach, was over-expressed in hindstomach epithelium of E11.5 Gata4(ki/ki) mice, and there was a concomitant decrease in fibroblast growth factor-10 in adjacent mesenchyme. We conclude that functional interaction between GATA-4 and a member of the FOG family, presumably FOG-1, is required for proper epithelial-mesenchymal signaling in the developing stomach.