Flanagan, D. J. et al. Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5+ stem cells. Stem Cell Reports 4, 759–767 (2015).
The extreme chemical and mechanical forces endured by the gastrointestinal tract drive a constant renewal of the epithelial lining. Stem cells of the intestine and stomach, marked by the cell surface receptor Lgr5, preserve the cellular status-quo of their respective tissues through receipt and integration of multiple cues from the surrounding niche. Wnt signalling is a critical niche component for gastrointestinal stem cells and we have previously shown that the Wnt receptor, Frizzled-7 (Fzd7), is required for gastric homeostasis and the function of Lgr5+ intestinal stem cells. Additionally, we have previously shown a requirement for the Wnt target gene Myc in intestinal homeostasis, regeneration and tumourigenesis. However, it is unknown whether Fzd7 or Myc have conserved functions in gastric Lgr5+ stem cells. Here we show that gastric Lgr5+ stem cells do not require Fzd7 or Myc and are able to maintain epithelial homeostasis, highlighting key differences in the way Wnt regulates homeostasis and Lgr5+ stem cells in the stomach compared to the intestinal epithelium. Furthermore, deletion of Myc throughout the epithelium of the gastric antrum has no deleterious effects suggesting therapeutic targeting of Myc in gastric cancer patients will be well tolerated by the surrounding normal tissue.
Funding is gratefully acknowledged from the following; National Health and Medical Research Council
of Australia (NHMRC, 566679 and APP1099302 awarded to E.V./T.P./N.B.), Melbourne Health project grants
(605030 and PG-002 awarded to E.V./T.P./N.B.), Medical Research Council (MR/R026424/1 to T.P.), and Early career researcher grant (GIA-033 awarded to D.F.), Cancer Council of Victoria project grants (CCV, APP1020716 awarded to E.V./T.P./N.B.), CCV Fellowship awarded to D.F. and Cardiff University/CMU Research Fellowship awarded to T.P.