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Loss of the Wnt Receptor Frizzled7 in the Gastric Epithelium is deleterious and triggers rapid repopulation in vivo

Flanagan, Dustin J, Barker, Nicholas, Nowell, Cameron, Clevers, Hans, Ernst, Matthias, Phesse, Toby and Vincan, Elizabeth 2017. Loss of the Wnt Receptor Frizzled7 in the Gastric Epithelium is deleterious and triggers rapid repopulation in vivo. Disease Models & Mechanisms 10 (8) , pp. 971-980. 10.1242/dmm.029876

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Abstract

The gastric epithelium consists of tubular glandular units, each containing several differentiated cell types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. 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 of 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 to identify potential points of therapeutic intervention. Wnt signalling regulates several cell functions, including proliferation, differentiation and migration, and plays a crucial 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 frizzled 7 (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 crucial role for Wnt signalling, via the Fzd7 receptor, during homeostasis of the gastric epithelium

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: Company of Biologists
ISSN: 1754-8403
Date of First Compliant Deposit: 8 June 2017
Date of Acceptance: 6 June 2017
Last Modified: 26 Nov 2018 10:35
URI: http://orca-mwe.cf.ac.uk/id/eprint/101318

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