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Title: Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo.
Austin Authors: Flanagan, Dustin J;Barker, Nick;Nowell, Cameron;Clevers, Hans;Ernst, Matthias ;Phesse, Toby J;Vincan, Elizabeth
Affiliation: Institute of Medical Biology, Singapore, Singapore
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia
Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, Netherlands
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
University of Melbourne and Victorian Infectious Diseases Reference Laboratory, Doherty Institute of Infection and Immunity, Melbourne, Victoria, Australia
European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, UK
School of Biomedical Sciences, Curtin University, Perth, WA, Australia
Issue Date: 1-Aug-2017
Date: 2017-06-09
Publication information: Disease models & mechanisms 2017; 10(8): 971-980
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.
DOI: 10.1242/dmm.029876
ORCID: 0000-0002-3915-8281
Journal: Disease models & mechanisms
PubMed URL: 28600348
Type: Journal Article
Subjects: Frizzled7
Gastric homeostasis
Appears in Collections:Journal articles

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