Wnt2/2b and β-Catenin Signaling Are Necessary and Sufficient to Specify Lung Progenitors in the Foregut

被引:337
作者
Goss, Ashley M. [1 ,2 ]
Tian, Ying [1 ,3 ]
Tsukiyama, Tadasuke [4 ]
Cohen, Ethan David [1 ,3 ]
Zhou, Diane [1 ,3 ]
Lu, Min Min [1 ,3 ]
Yamaguchi, Terry P. [4 ]
Morrisey, Edward E. [1 ,2 ,3 ,5 ]
机构
[1] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA
[3] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA
[4] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA
[5] Univ Penn, Inst Regenerat Med, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
ENHANCER-BINDING PROTEIN; LIVER GROWTH; WNT SIGNALS; MORPHOGENESIS; GENE; EPITHELIUM; PROLIFERATION; SPECIFICATION; DELETION; CELLS;
D O I
10.1016/j.devcel.2009.06.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 Writ 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.
引用
收藏
页码:290 / 298
页数:9
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