Frizzled7 Functions as a Wnt Receptor in Intestinal Epithelial Lgr5<SUP>+</SUP> Stem Cells

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Dustin J. Flanagan - , University of Melbourne, Victorian Infectious Diseases Reference Laboratory (Author)
  • Toby J. Phesse - , University of Melbourne (Author)
  • Nick Barker - , Agency for Science, Technology and Research, Singapore, University of Edinburgh (Author)
  • Renate H. M. Schwab - , University of Melbourne, Victorian Infectious Diseases Reference Laboratory (Author)
  • Nancy Amin - , University of Melbourne, Victorian Infectious Diseases Reference Laboratory (Author)
  • Jordane Malaterre - , Peter Maccallum Cancer Centre (Author)
  • Daniel E. Stange - , Department of Visceral, Thoracic and Vascular Surgery, Royal Netherlands Academy of Arts and Sciences (Author)
  • Cameron J. Nowell - , University of Melbourne (Author)
  • Scott A. Currie - , University of Melbourne, Victorian Infectious Diseases Reference Laboratory (Author)
  • Jarel T. S. Saw - , University of Melbourne, Victorian Infectious Diseases Reference Laboratory (Author)
  • Eva Beuchert - , University of Melbourne, Victorian Infectious Diseases Reference Laboratory (Author)
  • Robert G. Ramsay - , Peter Maccallum Cancer Centre (Author)
  • Owen J. Sansom - , Beatson Institute for Cancer Research (Author)
  • Matthias Ernst - , University of Melbourne (Author)
  • Hans Clevers - , Royal Netherlands Academy of Arts and Sciences (Author)
  • Elizabeth Vincan - , University of Melbourne, Victorian Infectious Diseases Reference Laboratory, Curtin University (Author)

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.

Details

Original languageEnglish
Pages (from-to)759-767
Number of pages9
JournalStem cell reports
Volume4
Issue number5
Publication statusPublished - 12 May 2015
Peer-reviewedYes

External IDs

PubMed 25892522
Scopus 84929270439

Keywords

Keywords

  • Signaling pathway, Gene-expression, Paneth cells, Beta-catenin, Regeneration, Myc, Maturation, Components, Deletion, Crypts