β-Catenin promotes respiratory progenitor identity in mouse foregut
β-Catenin promotes respiratory progenitor identity in mouse foregut
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DOI：
10.1073/pnas.0902274106
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发表时间：
2009-09-22
影响因子：
11.1
通讯作者：
Sun, Xin
中科院分区：
文献类型：
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作者：
Harris-Johnson, Kelley S.;Domyan, Eric T.;Sun, Xin
哺乳动物呼吸系统由气管和肺组成，起源于前肠内胚层。引导内胚层细胞分化为呼吸细胞命运的分子机制尚未完全清楚。在此我们发现，前肠内胚层中β -连环蛋白（也称为Ctnnb1）的条件性失活会导致气管和肺缺失，原因是无法维持呼吸细胞命运。相反，β -连环蛋白激活形式的条件性表达会使Nkx2.1（气管和肺的早期标志物）扩展到相邻的内胚层，包括胃上皮。对这些突变体的分析表明，气管/肺祖细胞特性的丧失或获得分别伴随着食管/胃祖细胞特性的扩张或收缩。我们的研究结果揭示了β -连环蛋白在小鼠前肠内胚层中呼吸祖细胞建立过程中的早期作用。
The mammalian respiratory system, consisting of both trachea and lung, initiates from the foregut endoderm. The molecular program that instructs endodermal cells to adopt the respiratory fate is not fully understood. Here we show that conditional inactivation of beta-Catenin (also termed Ctnnb1) in foregut endoderm leads to absence of both the trachea and lung due to a failure in maintaining the respiratory fate. In converse, conditional expression of an activated form of beta-Catenin leads to expansion of Nkx2.1, an early marker for the trachea and lung, into adjacent endoderm including the stomach epithelium. Analyses of these mutants show that the loss or gain of trachea/ lung progenitor identity is accompanied by an expansion or contraction of esophagus/stomach progenitor identity, respectively. Our findings reveal an early role for beta-Catenin in the establishment of respiratory progenitors in mouse foregut endoderm.