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A critical role for the Wnt effector Tcf4 in adult intestinal homeostatic self-renewal.

Throughout life, intestinal Lgr5+ stem cells give rise to proliferating transient amplifying cells in crypts, which subsequently differentiate into one of the five main cell types and migrate along the crypt-villus axis. These dynamic processes are coordinated by a relatively small number of evolutionarily conserved signaling pathways, which includes the Wnt signaling pathway. The DNA-binding proteins of the T-cell factor family, Tcf1/Tcf7, Lef, Tcf3/Tcf7l1, and Tcf4/Tcf7l2, constitute the downstream effectors of the Wnt signaling pathway. While Tcf4 is the major member active during embryogenesis, the role of these Wnt effectors in the homeostasis of the adult mouse intestinal epithelium is unresolved. Using Tcf1-/-, Tcf3(flox), and novel Tcf4(flox) mice, we demonstrate an essential role for Tcf4 during homeostasis of the adult mouse intestine.

Pubmed ID: 22393260


  • van Es JH
  • Haegebarth A
  • Kujala P
  • Itzkovitz S
  • Koo BK
  • Boj SF
  • Korving J
  • van den Born M
  • van Oudenaarden A
  • Robine S
  • Clevers H


Molecular and cellular biology

Publication Data

May 27, 2012

Associated Grants


Mesh Terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Differentiation
  • Cell Proliferation
  • Gene Expression Regulation, Developmental
  • Intestinal Mucosa
  • Intestines
  • Mice
  • Stem Cells
  • Wnt Signaling Pathway