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XB-ART-56304
Cell Rep January 1, 2019; 28 (13): 3338-3352.e6.

ΔN-Tp63 Mediates Wnt/β-Catenin-Induced Inhibition of Differentiation in Basal Stem Cells of Mucociliary Epithelia.

Haas M , Gómez Vázquez JL , Sun DI , Tran HT , Brislinger M , Tasca A , Shomroni O , Vleminckx K , Walentek P .


Abstract
Mucociliary epithelia provide a first line of defense against pathogens. Impaired regeneration and remodeling of mucociliary epithelia are associated with dysregulated Wnt/β-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/β-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.

PubMed ID: 31553905
PMC ID: PMC6935018
Article link: Cell Rep
Grant support: [+]
Genes referenced: ctnnb1 ctrl dkk1 foxa1 foxi1 foxj1 foxj1.2 h2bc21 krt61 mcc muc5b npat rspo2 tp63 znf469
GO keywords: Wnt signaling pathway [+]
Morpholinos: ctnnb1 MO1 tp63 MO3

Disease Ontology terms: chronic obstructive pulmonary disease

Article Images: [+] show captions
References [+] :
Antoniades, Making the connection: ciliary adhesion complexes anchor basal bodies to the actin cytoskeleton. 2014, Pubmed


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