Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.
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.
Goss
Ashley M
AM
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tian
Ying
Y
Tsukiyama
Tadasuke
T
Cohen
Ethan David
ED
Zhou
Diane
D
Lu
Min Min
MM
Yamaguchi
Terry P
TP
Morrisey
Edward E
EE
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D004064:Digestive System / Q000033:anatomy & histology / Q000196:embryology; D004707:Endoderm / Q000166:cytology / Q000502:physiology; D008168:Lung / Q000033:anatomy & histology / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051154:Wnt2 Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051153:Wnt Proteins; D051154:Wnt2 Protein; C492031:Wnt2b protein, mouse; D051176:beta Catenin
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