Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5 stem cells

DJ Flanagan; TJ Phesse; N Barker; RHM Schwab; N Amin; J Malaterre; DE Stange; CJ Nowell; SA Currie; JTS Saw; E Beuchert; RG Ramsay; OJ Sansom; M Ernst; H Clevers; E Vincan

Journal article

Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5 stem cells

DJ Flanagan, TJ Phesse, N Barker, RHM Schwab, N Amin, J Malaterre, DE Stange, CJ Nowell, SA Currie, JTS Saw, E Beuchert, RG Ramsay, OJ Sansom, M Ernst, H Clevers, E Vincan

Stem Cell Reports | Published : 2015

DOI: 10.1016/j.stemcr.2015.03.003

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Abstract

The mammalian adult small intestinal epithelium is a rapidly self-renewing tissue that is maintained by a pool of cycling stem cells intermingled with Paneth cells at the base of crypts. These crypt base stem cells exclusively express Lgr5 and require Wnt3 or, in its absence, Wnt2b. However, the Frizzled (Fzd) receptor that transmits these Wnt signals is unknown. We determined the expression profile of Fzd receptors in Lgr5+ stem cells, their immediate daughter cells, and Paneth cells. Here we show Fzd7 is enriched in Lgr5+ stem cells and binds Wnt3 and Wnt2b. Conditional deletion of the Fzd7 gene in adult intestinal epithelium leads to stem cell loss in vivo and organoid death in vitro. Cry..

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University of Melbourne Researchers

Toby Phesse Author

Rob Ramsay Author

Elizabeth Vincan Author

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Awarded by National Health and Medical Research Council

Funding Acknowledgements

We thank D.L. Neate and B.M. Tran for technical assistance. We thank A.R. Clarke for the AhCre mice and C.D. Mao for the expression plasmids. This work was supported by grants from NHMRC #566679 (E.V., N.B., H.C.), #603127 and #1025239 (T.J.P.), #1079257 (M.E.), and #487922 (M.E. and R.G.R.); Melbourne Health #605030 (E.V., N.B., T.J.P., H.C.), and the Cancer Council of Victoria (CCV) #APP1020716 (E.V., N.B., T.J.P., H.C.); and post-graduate awards from the CCV (D.J.F.) and Melbourne Health (R.H.M.S.). M.E. and R.G.R. are NHMRC Senior Research Fellows.