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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

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

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

OriginalspracheEnglisch
Seiten (von - bis)759-767
Seitenumfang9
FachzeitschriftStem cell reports
Jahrgang4
Ausgabenummer5
PublikationsstatusVeröffentlicht - 12 Mai 2015
Peer-Review-StatusJa

Externe IDs

PubMed 25892522
Scopus 84929270439

Schlagworte

Schlagwörter

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