Loss of GATA4 causes ectopic pancreas in the stomach

J Pathol. 2020 Apr;250(4):362-373. doi: 10.1002/path.5378. Epub 2020 Jan 20.

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 Gata4 flox/flox ; Pdx1-Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium displays an atypical morphology similar to the cornified squamous epithelium and exhibits 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. Of interest, the developing glands of the Gata4KO stomach express pancreatic cell markers. Furthermore, a mass of pancreatic tissue located in the subserosa of the Gata4KO stomach is observed at adult stages. Heterotopic pancreas found in Gata4-deficient mice contains all three pancreatic cell lineages: ductal, acinar, and endocrine. Moreover, Gata4 expression is downregulated in ectopic pancreatic tissue of some human biopsy samples. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: GATA4 transcription factor; glandular stomach; pancreas; pancreatic heterotopia; stomach development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Epithelial Cells / pathology*
  • GATA4 Transcription Factor / genetics*
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Mice, Transgenic
  • Organogenesis / physiology
  • Pancreas / pathology*

Substances

  • GATA4 Transcription Factor
  • GATA4 protein, human
  • Gata4 protein, mouse