Sox2 modulates Lef-1 expression during airway submucosal gland development

Area of Science:

• Molecular Biology
• Developmental Biology
• Epithelial Biology

Background:

• Tracheobronchial submucosal glands (SMGs) develop from airway stem cells.
• SMG formation involves placode development in the surface airway epithelium (SAE).
• Lymphoid enhancer factor-1 (Lef-1) gene expression is critical for SMG morphogenesis.

Purpose of the Study:

• To investigate the regulatory relationship between Sox2 and Lef-1 during SMG development.
• To determine the mechanism by which Sox2 influences Lef-1 expression.
• To elucidate the role of Sox2 in Wnt/β-catenin signaling during airway epithelial development.

Main Methods:

• Gene expression analysis (mRNA and protein levels).
• Reporter gene assays to assess promoter activity.
• Chromatin immunoprecipitation (ChIP) to identify DNA-protein interactions.
• Conditional gene deletion in primary airway epithelial cells.

Main Results:

• Sox2 protein levels decrease as Lef-1 is induced during SMG placode formation.
• Sox2 directly binds to the Lef-1 promoter and represses Wnt/β-catenin-dependent transcription.
• Wnt signaling enhances Lef-1 expression and inhibits Sox2 expression in airway epithelium.
• Sox2 deletion in airway epithelium increases Lef-1 expression, further enhanced by Wnt stimulation.

Conclusions:

• Sox2 acts as a direct transcriptional repressor of the Lef-1 gene.
• Wnt signaling and Sox2 dynamically regulate Lef-1 expression in airway epithelia.
• This regulatory axis is important for SMG development and airway epithelial homeostasis.