Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.

Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
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DOI:
10.1016/j.devcel.2009.06.005
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发表时间:
2009-08
期刊:
影响因子:
11.8
通讯作者:
Morrisey, Edward E.
Morrisey, Edward E.
中科院分区:
生物学1区
文献类型:
--
作者:
Goss, Ashley M.;Tian, Ying;Tsukiyama, Tadasuke;Cohen, Ethan David;Zhou, Diane;Lu, Min Min;Yamaguchi, Terry P.;Morrisey, Edward E.

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原始前肠以沿前后部轴线在空间上促进适当器官规格的方式被图案化。然而,前肠内胚层前体细胞的分子通路却知之甚少。我们发现Wnt2/2b信号是在前肠中指定肺内胚层前体细胞所必需的。Wnt2/2b表达缺失的胚胎表现为完全性肺发育不全,并且不表达肺内胚层最早的标志物Nkx2.1。相反,其他来自前肠内胚层的器官,包括甲状腺、肝脏和胰腺,在Wnt2/2b缺失动物中被正确地指定。我们表明,这种表型是由内胚层限制性的β-连环蛋白的缺失来概括的,表明通过典型的WNT途径的WNT2/2b信号是必需的,以指定前肠内的肺内胚祖细胞。此外,规范的Wnt/β-catenin信号的激活导致食道和胃内胚层重新编程为肺内胚层前体的命运。综上所述,这些数据表明,规范的WNT2/2b信号是在发育中的前庭指定肺内胚层前体细胞所唯一需要的。
The primitive foregut is patterned in a manner that spatially promotes proper organ specification along the anterior-posterior foregut axis. However, the molecular pathways that specify foregut endoderm progenitors are poorly understood. We show that Wnt2/2b signaling is required to specify lung endoderm progenitors within the anterior foregut. Embryos lacking Wnt2/2b expression exhibit complete lung agenesis and do not express Nkx2.1, the earliest marker of the lung endoderm. In contrast, other foregut endoderm derived organs including the thyroid, liver, and pancreas are correctly specified in Wnt2/2b null animals. We show that this phenotype is recapitulated by an endoderm restricted deletion of β-catenin, demonstrating that Wnt2/2b signaling through the canonical Wnt pathway is required to specify lung endoderm progenitors within the foregut. Moreover, activation of canonical Wnt/β-catenin signaling results in reprogramming of esophagus and stomach endoderm to a lung endoderm progenitor fate. Together, these data reveal that canonical Wnt2/2b signaling is uniquely required for specification of lung endoderm progenitors in the developing foregut.
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