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Stabilized beta-catenin in lung epithelial cells changes cell fate and leads to tracheal and bronchial polyposis.
- Source :
-
Developmental biology [Dev Biol] 2009 Oct 01; Vol. 334 (1), pp. 97-108. Date of Electronic Publication: 2009 Jul 23. - Publication Year :
- 2009
-
Abstract
- The precise mechanisms by which beta-catenin controls morphogenesis and cell differentiation remain largely unknown. Using embryonic lung development as a model, we deleted exon 3 of beta-catenin via Nkx2.1-cre in the Catnb[+/lox(ex3)] mice and studied its impact on epithelial morphogenesis. Robust selective accumulation of truncated, stabilized beta-catenin was found in Nkx2.1-cre;Catnb[+/lox(ex3)] lungs that were associated with the formation of polyp-like structures in the trachea and main-stem bronchi. Characterization of polyps suggests that accumulated beta-catenin impacts epithelial morphogenesis in at least two ways. "Intracellular" accumulation of beta-catenin blocked differentiation of spatially-appropriate airway epithelial cell types, Clara cells, ciliated cells and basal cells, and activated UCHL1, a marker for pulmonary neuroendocrine cells. There was also evidence for a "paracrine" impact of beta-catenin accumulation, potentially mediated via activation of Bmp4 that inhibited Clara and ciliated, but not basal cell differentiation. Thus, excess beta-catenin can alter cell fate determination by both direct and paracrine mechanisms.
- Subjects :
- Animals
Bone Morphogenetic Protein 4 metabolism
Cell Differentiation
Cells, Cultured
Fluorescent Antibody Technique
Genotype
Immunohistochemistry
In Situ Hybridization
Mice
Mice, Transgenic
Neuroendocrine Cells metabolism
Nuclear Proteins genetics
Nuclear Proteins metabolism
Signal Transduction
Thyroid Nuclear Factor 1
Transcription Factors genetics
Transcription Factors metabolism
Ubiquitin Thiolesterase metabolism
beta Catenin genetics
Bronchioles metabolism
Epithelial Cells metabolism
Lung metabolism
Trachea metabolism
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-564X
- Volume :
- 334
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 19631635
- Full Text :
- https://doi.org/10.1016/j.ydbio.2009.07.021