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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Enteroendocrine precursors differentiate independently of Wnt and form serotonin expressing adenomas in response to active β-catenin
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Enteroendocrine precursors differentiate independently of Wnt and form serotonin expressing adenomas in response to active β-catenin

机译：肠内分泌前体独立于Wnt分化并响应活性β-catenin形成表达5-羟色胺的腺瘤

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摘要

Wnt signaling is required for the maintenance of intestinal stem cells and self-renewal of the intestinal epithelium. Intestinal cancers are frequently associated with mutations that activate the Wnt pathway. The role of Wnt signaling on differentiation of lineage-specific precursors in the intestine is not well characterized. Here, we show that specification of enteroendocrine but not Paneth cells occurs independently of Wnt signals by conditional deletion of β-catenin in immature cells expressing the transcription factor, neurogenin 3. In addition, we determined whether neuro-genin 3-expressing cells respond to abnormal Wnt signaling. Activation of the Wnt pathway by conditionally deleting exon 3 of the β-catenin gene at an early stage of enteroendocrine cell differentiation induced small-intestinal adenomas expressing serotonin, a feature not previously described in other tumors induced by Wnt in mice. In contrast, excision of exon 3 of β-catenin at a later stage of enteroendocrine differentiation did not produce tumors. These results provide direct evidence that some intestinal lineages are specified independently of the Wnt pathway and may lead to a better understanding of the spectrum of neuroendocrine differentiation frequently seen in human gastrointestinal cancer.
机译：Wnt信号传导是维持肠干细胞和肠上皮自我更新所必需的。肠癌通常与激活Wnt途径的突变相关。 Wnt信号在肠中谱系特异性前体的分化中的作用尚未很好地表征。在这里，我们表明在表达转录因子神经生成素3的未成熟细胞中有条件地缺失β-catenin的情况下，肠内分泌而非Paneth细胞的出现独立于Wnt信号，此外，我们还确定了表达神经基因3的细胞是否响应Wnt信号异常。在肠内分泌细胞分化的早期阶段通过有条件地删除β-catenin基因的外显子3激活Wnt途径，从而诱导表达5-羟色胺的小肠腺瘤，这是以前在小鼠中由Wnt诱导的其他肿瘤中未描述的特征。相反，在肠内分泌分化的后期切除β-catenin的外显子3不会产生肿瘤。这些结果提供了直接证据，表明某些肠道谱系是独立于Wnt途径指定的，并且可能导致人们更好地了解人类胃肠道癌症中常见的神经内分泌分化谱。

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