Hindgut defects and transformation of the gastrointestinal tract in Tcf4-/-/Tcf1-/- embryos
Hindgut defects and transformation of the gastrointestinal tract in Tcf4-/-/Tcf1-/- embryos
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DOI：
10.1038/sj.emboj.7600191
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发表时间：
2004-04-21
期刊：
影响因子：
11.4
通讯作者：
Clevers, H
中科院分区：
文献类型：
--
作者：
Gregorieff, A;Grosschedl, R;Clevers, H
Wnt信号在发育过程中的前后轴的启动和模式化中起着关键作用。Wnt发挥其生物学效应，部分是通过TCF/LEF转录因子家族成员激活特异性靶基因。为了获得对T细胞因子（或Tcf）在发育过程中的作用的新认识，我们分析了Tcf 4和Tcf 1化合物无效胚胎。这些突变体表现出严重的尾部截断，以及重复的神经管。与其他影响Wnt信号的突变不同，近轴中胚层的形成没有受损，早期的尾标记物，如T，不受影响。内胚层标记物的分析揭示了早期和特定的缺陷，后肠扩张，后来的前转化的胃肠道。我们的研究结果揭示了Wnt信号在早期肠道形态发生中的新作用，并表明特定的Wnt驱动的图案化事件是由Tcf/Lef家族成员的独特组织分布决定的。
Wnt signalling plays a critical role in both initiating and patterning of the anterior-posterior axis during development. Wnts exert their biological effects, in part, by activating specific target genes through members of the TCF/LEF family of transcription factors. To gain new insight into the role of T-cell factors (or Tcf's) during development, we analysed Tcf4 and Tcf1 compound null embryos. These mutants showed severe caudal truncations, as well as duplications of the neural tube. Unlike other mutations affecting Wnt signalling, paraxial mesoderm formation was not impaired and early caudal markers, such as T, were unaffected. Analysis of endodermal markers uncovered early and specific defects in hindgut expansion, and later an anterior transformation of the gastro-intestinal tract. Our results reveal a novel role for Wnt signalling in early gut morphogenesis and suggest that specific Wnt-driven patterning events are determined by the unique tissue distribution of Tcf/Lef family members.