Loss of GATA4 causes ectopic pancreas in the stomach

Abstract

Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4flox/flox; Pdx1-Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium display an atypical morphology similar to the cornified squamous epithelium and exhibit upregulation of forestomach markers. The developing gastric units fail to form properly and the glandular epithelial cells do not express markers of gastric gland in the absence of GATA4. Interestingly, the developing glands of Gata4KO stomach express pancreatic cells markers. Furthermore, a mass of pancreatic tissue located in the subserosa of Gata4KO stomach is observed at adult stages. Heterotopic pancreas found in Gata4-deficient mice contains all three pancreatic cell lineages, ductal, acinar and endocrine cells. Moreover, Gata4 expression is downregulated in ectopic pancreatic tissue of some human biopsy samples.