Canonical Wnt signals are essential for homeostasis of the intestinal epithelium
Canonical Wnt signals are essential for homeostasis of the intestinal epithelium
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DOI：
10.1101/gad.267103
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发表时间：
2003-07-15
影响因子：
10.5
通讯作者：
Clevers, H
中科院分区：
文献类型：
--
作者：
Pinto, D;Gregorieff, A;Clevers, H
为了评估WRIT信号在肠道隐窝中的关键作用，我们制备了异位表达Wnt抑制因子Dickkopf 1(Dkk1)的转基因小鼠。我们发现上皮细胞的增殖大大减少，这与隐窝的丧失不谋而合。虽然肠细胞分化似乎没有受到影响，但分泌细胞谱系在很大程度上缺失。肠道动态平衡的破坏反映为缺乏核β-连环素，抑制c-myc的表达，随后上调p21(CIP1/WAF1)。因此，我们的数据首次建立了对WRIT配体在驱动肠上皮细胞增殖方面的直接要求，并定义了WRIT在控制分泌细胞分化方面的意想不到的作用。
To assess the critical role of Writ signals in intestinal crypts, we generated transgenic mice ectopically expressing Dickkopf 1 (Dkk1), a secreted Wnt inhibitor. We find that epithelial proliferation is greatly reduced coincidentally with the loss of crypts. Although enterocyte differentiation appears unaffected, secretory cell lineages are largely absent. Disrupted intestinal homeostasis is reflected by an absence of nuclear beta-catenin, inhibition of c-myc expression, and subsequent up-regulation of p21(CIP1/WAF1). Thus, our data are the first to establish a direct requirement for Writ ligands in driving proliferation in the intestinal epithelium, and also define an unexpected role for Writs in controlling secretory cell differentiation.