Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo

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Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo
Title:
Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo
Journal Title:
Disease Models & Mechanisms
Keywords:
Publication Date:
02 August 2017
Citation:
Flanagan, D. J. et al. Loss of the Wnt receptor frizzled 7 in the mouse gastric epithelium is deleterious and triggers rapid repopulation in vivo. Dis. Model. Mech. 10, 971–980 (2017)
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
Funding is gratefully acknowledged from the following: National Health and Medical Research Council of Australia (566679 and APP1099302); Melbourne Health project grants (605030 and PG-002) and early career researcher grant (GIA-033) awarded to D.J.F.; Cancer Council Victoria project grants (APP1020716) awarded to E.V. and T.J.P.; Cancer Council Victoria Fellowship awarded to D.J.F.; and a Cardiff University Research Fellowship awarded to T.J.P.
Description:
ISSN:
1754-8403
1754-8411
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