Flanagan, D. J. et al. (2015) Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5+ stem cells. Stem Cell Reports, 4(5), pp. 759-767. (doi: 10.1016/j.stemcr.2015.03.003) (PMID:25892522) (PMCID:PMC4437483)
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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. Crypts of conventional Fzd7 knockout mice show decreased basal Wnt signaling and impaired capacity to regenerate the epithelium following deleterious insult. These observations indicate that Fzd7 is required for robust Wnt-dependent processes in Lgr5+ intestinal stem cells.
| Item Type: | Articles |
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| Additional Information: | 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. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Sansom, Professor Owen |
| Authors: | Flanagan, D. J., Phesse, T. J., Barker, N., Schwab, R. H.M., Amin, N., Malaterre, J., Stange, D. E., Nowell, C. J., Currie, S. A., Saw, J. T.S., Beuchert, E., Ramsay, R. G., Sansom, O. J., Ernst, M., Clevers, H., and Vincan, E. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Stem Cell Reports |
| Publisher: | Elsevier |
| ISSN: | 2213-6711 |
| ISSN (Online): | 2213-6711 |
| Published Online: | 16 April 2015 |
| Copyright Holders: | Copyright © 2015 The Authors |
| First Published: | First published in Stem Cell Reports 4(5):759-767 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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