Expression pattern of Wnt signaling components in the adult intestine
Expression pattern of Wnt signaling components in the adult intestine
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DOI：
10.1053/j.gastro.2005.06.007
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发表时间：
2005-08-01
期刊：
影响因子：
29.4
通讯作者：
Clevers, H
中科院分区：
文献类型：
--
作者：
Gregorieff, A;Pinto, D;Clevers, H
背景和目的：在肠道中，规范的书面信号传导级联对于驱动上皮细胞的增殖起着至关重要的作用。此外，令状信号的异常激活与大肠癌的发展密切相关。尽管有这样的证据，但对成人肠中令状及其下游效应子的精确身份和定位知之甚少。为了解决这个问题，我们检查了所有令状，卷曲（FZS），低密度脂蛋白受体相关蛋白，与书面拮抗剂和T细胞因子的表达模式。方法：通过使用特定的RNA探针对所测试的各种基因，对胚胎，产后和成年肠样品进行原位杂交进行原位杂交。结果：我们的分析表明，几种信号传导成分（包括Wnt-3，Wnt-6，Wnt-9b，毛躁4，卷曲6，卷曲7，低密度脂蛋白受体相关蛋白5和分泌的毛躁相关蛋白质5）在隐窝上皮细胞中。我们还检测到WNT-2B，WNT-4，WNT-5A，WNT-5B，毛躁4，在小肠和结肠的分化上皮细胞和间质细胞中毛躁4。最后，几个因素（毛躁4，T细胞因子：1，淋巴样增强子因子，Dickkopf 2，Dickkopf 3和Wnt-Contracting因子）在正常的肿瘤组织中显示出差异的表达。结论：我们的研究预测，在肠道发育和稳态中，与以前在可用的遗传研究中预期的，在肠道发展和体内平衡中的作用要大得多，并确定了促进肠道中促进规范和非规范笔迹的新因素。
Background & Aims: In the intestine, the canonical Writ signaling cascade plays a crucial role in driving the proliferation of epithelial cells. Furthermore, aberrant activation of Writ signaling is strongly associated with the development of colorectal cancer. Despite this evidence, little is known about the precise identity and localization of Writs and their downstream effectors in the adult intestine. To address this issue, we examined the expression pattern of all Writs, Frizzleds (Fzs), low-density lipoprotein receptor-related proteins, Writ antagonists, and T-cell factors in the murine small intestine and colon and adenomas. Methods: Embryonic, postnatal, and adult intestinal samples were subjected to in situ hybridization by using specific RNA probes for the various genes tested. Results: Our analysis showed high expression of several signaling components (including Wnt-3, Wnt-6, Wnt-9b, Frizzled 4, Frizzled 6, Frizzled 7, low-density lipoprotein receptor-related protein 5, and secreted Frizzled-related protein 5) in crypt epithelial cells. We also detected Wnt-2b, Wnt-4, Wnt-5a, Wnt-5b, Frizzled 4, and Frizzled 6 in differentiated epithelial and mesenchymal cells of the small intestine and colon. Finally, several factors (Frizzled 4, T-cell factor :1, lymphoid enhancer factor, Dickkopf 2, Dickkopf 3, and Wnt-interacting factor) displayed differential expression in normal vs neoplastic tissue. Conclusions: Our study predicts a much broader role for Writ signaling in gut development and homeostasis than was previously anticipated from available genetic studies and identifies novel factors likely involved in promoting canonical and noncanonical Writ signals in the intestine.