Article

β-Catenin-SOX2 signaling regulates the fate of developing airway epithelium

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, 106 Research Drive, 2075 MSRBII, DUMC Box 103000, Durham, NC, 27710, USA.
Journal of Cell Science (Impact Factor: 5.33). 03/2012; 125(Pt 4):932-42. DOI: 10.1242/jcs.092734
Source: PubMed

ABSTRACT Wnt-β-catenin signaling regulates cell fate during organ development and postnatal tissue maintenance, but its contribution to specification of distinct lung epithelial lineages is still unclear. To address this question, we used a Cre recombinase (Cre)-LoxP approach to activate canonical Wnt signaling ectopically in developing lung endoderm. We found that persistent activation of canonical Wnt signaling within distal lung endoderm was permissive for normal development of alveolar epithelium, yet led to the loss of developing bronchiolar epithelium and ectasis of distal conducting airways. Activation of canonical Wnt led to ectopic expression of a lymphoid-enhancing factor and a T-cell factor (LEF and TCF, respectively) and absence of SRY (sex-determining region Y)-box 2 (SOX2) and tumor protein p63 (p63) expression in proximal derivatives. Conditional loss of SOX2 in airways phenocopied epithelial differentiation defects observed with ectopic activation of canonical Wnt. Our data suggest that Wnt negatively regulates a SOX2-dependent signaling program required for developmental progression of the bronchiolar lineage.

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    • "The molecular phenotypes of developing proximal and distal lung epithelial cell lineages have been associated with the differential expression of the transcription factors Sox2 and Sox9—sex-determining region Y (SRY)-box 2 and 9 [31]. Sox genes are highly conserved throughout the animal kingdom [32] and Sox2 has been implicated as an early marker for proximal lung cell differentiation [33] whereas Sox9 has been increasingly connected with distal respiratory trajectories [34]. "
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