Loss of the Wnt receptor Frizzled7 in the gastric epithelium is deleterious and triggers rapid repopulation in vivo

Dustin J Flanagan, Nicholas Barker, Cameron Nowell, Hans Clevers, Matthias Ernst, Toby J Phesse, Elizabeth Vincan

Research output: Contribution to journalArticlepeer-review

Abstract

The gastric epithelium consists of tubular glandular units each containing several differentiated cells types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Cell signalling provides cues to regulate development and homeostasis of adult tissues, however very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation to signalling pathways that regulate homeostasis of the diseased organ. Therefore it is important to understand the biology of how normal conditions are maintained in a tissue to help inform the mechanisms driving disease in that same tissue, and identify potential points of therapeutic intervention. Wnt signalling regulates several cell functions including proliferation, differentiation and migration, and plays a critical role during homeostasis of several tissues, including the intestinal epithelium. Wnt3a is required in the culture medium of gastric organoids, suggesting it is also important for the homeostasis of the gastric epithelium, but this has not been investigated in vivo Here we show that the Wnt receptor Frizzled7 (Fzd7), which is required for the homeostasis of the intestine, is expressed in the gastric epithelium and is required for gastric organoid growth. Gastric specific loss of Fzd7 in the adult gastric epithelium of mice is deleterious and triggers rapid epithelial repopulation, which we believe is the first observation of this novel function for this tissue. Taken together these data provide functional evidence of a critical role for Wnt signalling, via the Fzd7 receptor, during homeostasis of the gastric epithelium.

Original languageEnglish
JournalDisease Models and Mechanisms
Early online date9 Jun 2017
DOIs
Publication statusE-pub ahead of print - 9 Jun 2017

Keywords

  • Journal Article

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