?-catenin dosage is a critical determinant of tracheal basal cell fate determination.

ABSTRACT: The purpose of this study was to determine whether ?-catenin regulates basal cell fate determination in the mouse trachea. Analysis of TOPGal transgene reporter activity and Wnt/?-catenin pathway gene expression suggested a role for ?-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 ?-catenin. This issue was overcome by analysis of ?-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 ?-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 ?-catenin in basal to ciliated and basal to Clara-like cell differentiation. Genetic stabilization of ?-catenin in basal cells shortened the period of basal cell proliferation but had a minor effect on this process. Persistent ?-catenin signaling regulated basal cell fate by driving the generation of ciliated cells and preventing the production of Clara-like cells.

SUBMITTER: Brechbuhl HM 

PROVIDER: S-EPMC3123883 | biostudies-other | 2011 Jul

REPOSITORIES: biostudies-other