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

Johan H. van Es, Andrea Haegebarth, Pekka Kujala, Shalev Itzkovitz, Bon Kyoung Koo, Sylvia F. Boj, Jeroen Korving, Maaike van den Born, Alexander van Oudenaarden, Sylvie Robin, Hans Clevers

Research output: Contribution to journalArticlepeer-review

213 Citations (Scopus)

Abstract

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-/-, Tcf3flox, and novel Tcf4flox mice, we demonstrate an essential role for Tcf4 during homeostasis of the adult mouse intestine.

Original languageEnglish
Pages (from-to)1918-1927
Number of pages10
JournalMolecular and Cellular Biology
Volume32
Issue number10
DOIs
Publication statusPublished - May 2012
Externally publishedYes

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