| First Author | Smith MK | Year | 2012 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 302 |
| Issue | 6 | Pages | L580-94 |
| PubMed ID | 22227204 | Mgi Jnum | J:183435 |
| Mgi Id | MGI:5318662 | Doi | 10.1152/ajplung.00095.2011 |
| Citation | Smith MK, et al. (2012) Direct and indirect roles for beta-catenin in facultative basal progenitor cell differentiation. Am J Physiol Lung Cell Mol Physiol 302(6):L580-94 |
| abstractText | The conducting airway epithelium is maintained and repaired by endogenous progenitor cells. Dysregulated progenitor cell proliferation and differentiation is thought to contribute to epithelial dysplasia in chronic lung disease. Thus modification of progenitor cell function is an attractive therapeutic goal and one that would be facilitated by knowledge of the molecular pathways that regulate their behavior. We modeled the human tracheobronchial epithelium using primary mouse tracheal epithelial cell cultures that were differentiated by exposure to the air-liquid-interface (ALI). A basal cell subset, termed facultative basal cell progenitors (FBP), initiate these cultures and are the progenitor for tracheal-specific secretory cells, the Clara-like cell, and ciliated cells. To test the hypothesis that beta-catenin is necessary for FBP function, ALI cultures were generated from mice homozygous for the Ctnb(flox(E2-6)) allele. In this model, exons 2-6 of the beta-catenin gene are flanked by LoxP sites, allowing conditional knockout of beta-catenin. The beta-catenin locus was modified through transduction with Adenovirus-5-encoding Cre recombinase. This approach generated a mosaic epithelium, comprised of beta-catenin wild-type and beta-catenin knockout cells. Dual immunostaining and quantitative histomorphometric analyses demonstrated that beta-catenin played a direct role in FBP-to-ciliated cell differentiation and that it regulated cell-cell interactions that were necessary for FBP-to-Clara-like cell differentiation. beta-catenin was also necessary for FBP proliferation and long-term FBP viability. We conclude that beta-catenin is a critical determinant of FBP function and suggest that dysregulation of the beta-catenin signaling pathway may contribute to disease pathology. |
