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
影响因子:
11.8
通讯作者:
Morrisey, Edward E.
中科院分区:
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.
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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