[PDF][PDF] Wnt2/2b and β-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut

AM Goss, Y Tian, T Tsukiyama, ED Cohen, D Zhou… - Developmental cell, 2009 - cell.com
AM Goss, Y Tian, T Tsukiyama, ED Cohen, D Zhou, MM Lu, TP Yamaguchi, EE Morrisey
Developmental cell, 2009cell.com
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 …
Summary
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 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 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.
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