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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mapping Wnt/β-catenin signaling during mouse development and in colorectal tumors
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Mapping Wnt/β-catenin signaling during mouse development and in colorectal tumors

机译：在小鼠发育过程中和结肠直肠肿瘤中定位Wnt /β-catenin信号转导

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Wnt/β-catenin signaling plays key roles in several developmental and pathological processes. Domains of Wnt expression have been extensively investigated in the mouse, but the tissues receiving the signal remain largely unidentified. To define which cells respond to activated β-catenin during mammalian development, we generated the β-catenin-activated transgene driving expression of nuclear β-galactosidase reporter (BAT-gal) transgenic mice, expressing the lacZ gene under the control of β-catenin/T cell factor responsive elements. Reporter gene activity is found in known organizing centers, such as the midhindbrain border and the limb apical ectodermal ridge. Moreover, BAT-gal expression identifies novel sites of Wnt signaling, like notochord, endothelia, and areas of the adult brain, revealing an unsuspected dynamic pattern of β-catenin transcriptional activity. Expression of the transgene was analyzed in mutant backgrounds. In lipoprotein receptor-related protein 6-null homozygous mice, which lack a Wnt coreceptor, BAT-gal staining is absent in mutant tissues, indicating that BAT-gal mice are bona fide in vivo indicators of Wnt/β-catenin signaling. Analyses of BAT-gal expression in the adenomatous polyposis coli (multiple intestinal neoplasia/+) background revealed β-catenin transcriptional activity in intestinal adenomas but surprisingly not in normal crypt cells. In summary, BAT-gal mice unveil the entire complexity of Wnt/β-catenin signaling in mammals and have broad application potentials for the identification of Wnt-responsive cell populations in development and disease.
机译：Wnt /β-catenin信号传导在一些发育和病理过程中起关键作用。 Wnt表达域已在小鼠中进行了广泛研究，但接收信号的组织很大程度上仍未被确认。为了确定在哺乳动物发育过程中哪些细胞对活化的β-catenin有反应，我们产生了β-catenin活化的转基因，驱动核β-半乳糖苷酶报告基因（BAT-gal）转基因小鼠的表达，并在β-catenin的控制下表达lacZ基因/ T细胞因子反应元件。在已知的组织中心，例如中脑后缘和四肢顶端外胚层脊中发现了记者基因的活性。此外，BAT-gal表达可识别Wnt信号传导的新位点，例如脊索，内皮和成人大脑区域，从而揭示了β-catenin转录活性的动态模式。在突变背景中分析了转基因的表达。在缺少Wnt共受体的脂蛋白受体相关蛋白6空纯合小鼠中，突变组织中不存在BAT-gal染色，这表明BAT-gal小鼠是Wnt /β-catenin信号传导的真正体内指示剂。对腺瘤性息肉病大肠杆菌（多肠肿瘤/ +）背景中BAT-gal表达的分析显示，β-catenin在肠腺瘤中有转录活性，但令人惊讶的是在正常隐窝细胞中没有。总之，BAT-gal小鼠揭示了哺乳动物中Wnt /β-catenin信号传导的全部复杂性，在鉴定发育和疾病中Wnt反应细胞群方面具有广泛的应用潜力。

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