Wnt2/2b和β-连环蛋白信号对于在前肠中确定肺祖细胞是必要且充分的。
Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
作者信息
Goss Ashley M, Tian Ying, Tsukiyama Tadasuke, Cohen Ethan David, Zhou Diane, Lu Min Min, Yamaguchi Terry P, Morrisey Edward E
机构信息
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Dev Cell. 2009 Aug;17(2):290-8. doi: 10.1016/j.devcel.2009.06.005.
Patterning of the primitive foregut promotes appropriate organ specification along its anterior-posterior axis. However, the molecular pathways specifying foregut endoderm progenitors are poorly understood. We show here 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. The phenotype observed is recapitulated by an endoderm-restricted deletion of beta-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/beta-catenin signaling results in the reprogramming of esophagus and stomach endoderm to a lung endoderm progenitor fate. Together, these data reveal that canonical Wnt2/2b signaling is required for the specification of lung endoderm progenitors in the developing foregut.
原始前肠的模式形成促进了沿其前后轴的适当器官特化。然而，关于确定前肠内胚层祖细胞的分子途径却知之甚少。我们在此表明，Wnt2/2b信号传导是确定前肠前部肺内胚层祖细胞所必需的。缺乏Wnt2/2b表达的胚胎表现出完全的肺发育不全，且不表达Nkx2.1，即肺内胚层最早的标志物。相反，其他源自前肠内胚层的器官，包括甲状腺、肝脏和胰腺，都能正确特化。通过内胚层特异性缺失β-连环蛋白可重现所观察到的表型，这表明通过经典Wnt途径的Wnt2/2b信号传导是确定前肠内肺内胚层祖细胞所必需的。此外，经典Wnt/β-连环蛋白信号传导的激活会导致食管和胃内胚层重编程为肺内胚层祖细胞命运。总之，这些数据表明，经典Wnt2/2b信号传导是发育中的前肠中肺内胚层祖细胞特化所必需的。
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