title: β-catenin dosage is a critical determinant of tracheal basal cell fate determination.
abstract: The purpose of this study was to determine whether β-catenin regulates basal cell fate determination in the mouse trachea. Analysis of TOPGal transgene reporter activity and Wnt/β-catenin pathway gene expression suggested a role for β-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 β-catenin. This issue was overcome by analysis of β-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 β-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 β-catenin in basal to ciliated and basal to Clara-like cell differentiation. Genetic stabilization of β-catenin in basal cells shortened the period of basal cell proliferation but had a minor effect on this process. Persistent β-catenin signaling regulated basal cell fate by driving the generation of ciliated cells and preventing the production of Clara-like cells.
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO80206, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Brechbuhl
authors.forename: Moumita
authors.initials: M
authors.lastname: Ghosh
authors.forename: Mary Kathryn
authors.initials: MK
authors.lastname: Smith
authors.forename: Russell W
authors.initials: RW
authors.lastname: Smith
authors.forename: Bilan
authors.initials: B
authors.lastname: Li
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Hicks
authors.forename: Brook B
authors.initials: BB
authors.lastname: Cole
authors.forename: Paul R
authors.initials: PR
authors.lastname: Reynolds
authors.forename: Susan D
authors.initials: SD
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002923:Cilia / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009281:Naphthalenes / Q000008:administration & dosage*; D020411:Oligonucleotide Array Sequence Analysis; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D019076:Transgenes / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009281:Naphthalenes; D051176:beta Catenin; C031721:naphthalene; D001616:beta-Galactosidase