| First Author | Brechbuhl HM | Year | 2011 |
| Journal | Am J Pathol | Volume | 179 |
| Issue | 1 | Pages | 367-79 |
| PubMed ID | 21703416 | Mgi Jnum | J:173999 |
| Mgi Id | MGI:5050765 | Doi | 10.1016/j.ajpath.2011.03.016 |
| Citation | Brechbuhl HM, et al. (2011) beta-Catenin Dosage Is a Critical Determinant of Tracheal Basal Cell Fate Determination. Am J Pathol 179(1):367-79 |
| abstractText | The purpose of this study was to determine whether beta-catenin regulates basal cell fate determination in the mouse trachea. Analysis of TOPGal transgene reporter activity and Wnt/beta-catenin pathway gene expression suggested a role for beta-catenin in basal cell proliferation and differentiation after naphthalene-mediated Clara-like and ciliated cell depletion. However, these basal cell activities occurred simultaneously, limiting precise determination of the role(s) played by beta-catenin. This issue was overcome by analysis of beta-catenin signaling in tracheal air-liquid interface cultures. The cultures could be divided into two phases: basal cell proliferation and basal cell differentiation. A role for beta-catenin in basal cell proliferation was indicated by activation of the TOPGal transgene on proliferation days 3 to 5 and by transient expression of Myc (alias c-myc). Another peak of TOPGal transgene activity was detected on differentiation days 2 to 10 and was associated with the expression of Axin 2. These results suggest a role for beta-catenin in basal to ciliated and basal to Clara-like cell differentiation. Genetic stabilization of beta-catenin in basal cells shortened the period of basal cell proliferation but had a minor effect on this process. Persistent beta-catenin signaling regulated basal cell fate by driving the generation of ciliated cells and preventing the production of Clara-like cells. |
