title: A critical role for the Wnt effector Tcf4 in adult intestinal homeostatic self-renewal.
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-/-, Tcf3(flox), and novel Tcf4(flox) mice, we demonstrate an essential role for Tcf4 during homeostasis of the adult mouse intestine.
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.forename: Andrea
authors.initials: A
authors.lastname: Haegebarth
authors.forename: Pekka
authors.initials: P
authors.lastname: Kujala
authors.forename: Shalev
authors.initials: S
authors.lastname: Itzkovitz
authors.forename: Bon-Kyoung
authors.initials: BK
authors.lastname: Koo
authors.forename: Sylvia F
authors.initials: SF
authors.lastname: Boj
authors.forename: Jeroen
authors.initials: J
authors.lastname: Korving
authors.forename: Maaike
authors.initials: M
authors.lastname: van den Born
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robine
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000073940:Transcription Factor 4; D060449:Wnt Signaling Pathway
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4