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

Abstract

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. Developmental Dynamics 234:355-362, 2005.

Direct transcriptional regulation of Gata4 during early endoderm specification is controlled by FoxA2 binding to an intronic enhancer

“…3D). These results are in agreement with the previously described expression of endogenous Gata4 in the developing stomach (Jacobsen et al, 2005). In the dorsal pancreas, only a few cells in the epithelium displayed detectable β-galactosidase activity at E13.5 (Fig.…”

GATA4 and GATA6 regulate pancreatic endoderm identity through inhibition of hedgehog signaling

“…In addition, there was a notable upregulation of many components of the hedgehog pathway, suggesting that the major mechanism of GATA4/6-regulated pancreas development is through suppression of the hedgehog pathway. Previous studies have demonstrated that GATA factors can negatively regulate Shh expression in the stomach, limb bud, and somites (Daoud et al, 2014;Jacobsen et al, 2005;Kozhemyakina et al, 2014). Our studies suggest that GATA4 and GATA6 pattern the foregut endoderm through the repression of hedgehog signaling.…”

“…During gastric development, Gata4 and Shh expression is mutually exclusive, suggesting that GATA4 might inhibit the expression of Shh (Jacobsen et al, 2005). In the limb bud, GATA6 was shown to inhibit Shh gene expression through a limb bud-specific enhancer of the Shh gene , and in the somitic system, GATA4/5/6 were found to inhibit Shh signaling by inhibiting Gli1 expression, although direct inhibition of Shh was not required (Daoud et al, 2014).…”

Regulatory crosstalk between lineage-survival oncogenesKLF5, GATA4andGATA6cooperatively promotes gastric cancer development

“…Prior evidence suggests that KLF5 , GATA4 and GATA6 are primarily involved in cancers of the GI tract. In GC, GATA4 and GATA6 are expressed in the developing stomach35 and may be regulated by DNA methylation 36. Similarly, KLF5 expression in GCs can be induced by Helicobacter pylori infection and metaplasia-inducing factors such as CDX1 37 38.…”