Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Utrecht, Netherlands.
Mol Cell Biol. 2012 May;32(10):1918-27. doi: 10.1128/MCB.06288-11. Epub 2012 Mar 5.
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.
在整个生命过程中，肠道 Lgr5+干细胞在隐窝中产生增殖的短暂扩增细胞，这些细胞随后分化为五种主要细胞类型之一，并沿着隐窝-绒毛轴迁移。这些动态过程由相对较少的进化保守信号通路协调，其中包括 Wnt 信号通路。T 细胞因子家族的 DNA 结合蛋白 Tcf1/Tcf7、Lef、Tcf3/Tcf7l1 和 Tcf4/Tcf7l2 构成了 Wnt 信号通路的下游效应物。虽然 Tcf4 是胚胎发生过程中主要的活性成员，但这些 Wnt 效应物在成年小鼠肠道上皮细胞的稳态中的作用尚未解决。利用 Tcf1-/-、Tcf3(flox) 和新型 Tcf4(flox) 小鼠，我们证明了 Tcf4 在成年小鼠肠道的稳态中起着至关重要的作用。
