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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 Gata4ki/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 Gata4ki/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. Developmental Dynamics 234:355–362, 2005. © 2005 Wiley‐Liss, Inc.