Cdx function is required for maintenance of intestinal identity in the adult
Cdx function is required for maintenance of intestinal identity in the adult
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DOI：
10.1016/j.ydbio.2012.01.010
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发表时间：
2012-03-15
影响因子：
2.7
通讯作者：
Lohnes, David
中科院分区：
文献类型：
--
作者：
Hryniuk, Alexa;Grainger, Stephanie;Lohnes, David
同源结构域转录因子Cdx1和Cdx2在肠上皮中从早期发育开始表达，并且在动物的整个生命中持续表达。虽然我们对Cdx成员在肠道发育中的功能的理解已经取得了显着进展，但它们在成人肠道中的作用相对知之甚少。在本研究中，我们发现，在成年小肠中Cdx2的消融严重影响绒毛形态，增殖和肠道基因表达模式，导致动物死亡。在嵌合模型中Cdx2的长期丢失导致所有分化的肠细胞类型的丢失和粘膜向胃样上皮的部分转化。Cdx1的伴随损失并没有加剧任何这些表型。结肠中Cdx2的丢失与盲肠样上皮形态的转变和盲肠相关基因的获得相关，这在随后的Cdx1丢失中更为明显。这些研究结果表明，Cdx2是必不可少的小肠上皮细胞的分化，Cdx1和Cdx2有助于结肠的稳态。(C)2012 Elsevier Inc. All rights reserved.
The homeodomain transcription factors Cdx1 and Cdx2 are expressed in the intestinal epithelium from early development, with expression persisting throughout the life of the animal. While our understanding of the function of Cdx members in intestinal development has advanced significantly, their roles in the adult intestine is relatively poorly understood. In the present study, we found that ablation of Cdx2 in the adult small intestine severely impacted villus morphology, proliferation and intestinal gene expression patterns, resulting in the demise of the animal. Long-term loss of Cdx2 in a chimeric model resulted in loss of all differentiated intestinal cell types and partial conversion of the mucosa to a gastric-like epithelium. Concomitant loss of Cdx1 did not exacerbate any of these phenotypes. Loss of Cdx2 in the colon was associated with a shift to a cecum-like epithelial morphology and gain of cecum-associated genes which was more pronounced with subsequent loss of Cdx1. These findings suggest that Cdx2 is essential for differentiation of the small intestinal epithelium, and that both Cdx1 and Cdx2 contribute to homeostasis of the colon. (C) 2012 Elsevier Inc. All rights reserved.