[Delta]N-Tp63 mediates Wnt/[beta]-catenin-induced inhibition of differentiation in basal stem cells of mucociliary epithelia

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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Cell reports. - 28, 13 (2019) , 3338-3352.e6, ISSN: 2211-1247

Classification
Biowissenschaften, Biologie
Keyword
Basalzelle
Epithel
Krallenfrosch
Maus

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2019
Creator
Haas, Maximilian
Gómez Vázquez, José Luis
Sun, Dingyuan Iris
Tran, Hong Thi
Brislinger, Magdalena Maria
Tasca, Alexia
Shomroni, Orr
Vleminckx, Kris
Walentek, Peter

DOI
10.1016/j.celrep.2019.08.063
URN
urn:nbn:de:bsz:25-freidok-1510756
Rights
Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
25.03.2025, 1:47 PM CET

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Associated

Time of origin

  • 2019

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