ΔN-Tp63 Mediates Wnt/ß-Catenin-Induced Inhibition of Differentiation in Basal Stem Cells of Mucociliary Epithelia.
Cell Rep
; 28(13): 3338-3352.e6, 2019 09 24.
Article
in En
| MEDLINE
| ID: mdl-31553905
ABSTRACT
Mucociliary epithelia provide a first line of defense against pathogens. Impaired regeneration and remodeling of mucociliary epithelia are associated with dysregulated Wnt/ß-catenin signaling in chronic airway diseases, but underlying mechanisms remain elusive, and studies yield seemingly contradicting results. Employing the Xenopus mucociliary epidermis, the mouse airway, and human airway Basal cells, we characterize the evolutionarily conserved roles of Wnt/ß-catenin signaling in vertebrates. In multiciliated cells, Wnt is required for cilia formation during differentiation. In Basal cells, Wnt prevents specification of epithelial cell types by activating ΔN-TP63, a master transcription factor, which is necessary and sufficient to mediate the Wnt-induced inhibition of specification and is required to retain Basal cells during development. Chronic Wnt activation leads to remodeling and Basal cell hyperplasia, which are reversible in vivo and in vitro, suggesting Wnt inhibition as a treatment option in chronic lung diseases. Our work provides important insights into mucociliary signaling, development, and disease.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Tumor Suppressor Proteins
/
Epithelium
/
Beta Catenin
/
Wnt Signaling Pathway
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2019
Document type:
Article