Evolution of mechanotransduction via YAP/TAZ in animal epitheliaMore about Open Access at the Crick
Authors listAhmed Elbediwy Barry J Thompson
Mechanical stretch forces can control the growth of epithelial tissues such as mammalian skin, whose surface area is precisely coordinated with body size. In skin keratinocytes cultured in vitro, mechanical forces acting via Integrin adhesions and the actin cytoskeleton have been shown to induce nuclear translocation of YAP/TAZ co-activators to induce cell proliferation. Furthermore, conditional knockouts of both YAP (also called YAP1) and TAZ (also called WWTR1) in mouse skin resemble the phenotype of skin-specific loss of Integrin beta1 (ITGB1), indicating that this signalling mechanism is important in vivo. Curiously, Integrins are dispensable in Drosophila to activate the sole YAP/TAZ homolog Yorkie (Yki), which has lost the C-terminal PDZ-binding motif needed to promote nuclear localization of YAP/TAZ in mammalian cells. Differences in the structure of the epidermis between deuterostomes (e.g.: stratified squamous skin of mammals) and protostomes (e.g.: monolayered columnar epidermis of Drosophila) may explain this evolutionary divergence. Monolayered columnar epithelia feature a well-differentiated apical membrane domain, where proteins such as Crumbs, Expanded, Merlin and Kibra activate the Hippo pathway to repress Drosophila Yki. Stratified squamous epithelia lack an apical domain and thus depend primarily on basal Integrin adhesions to activate YAP/TAZ in basal layer stem cells via multiple postulated signalling mechanisms. Finally, YAP and TAZ retain the ability to sense the apical domain in the columnar epithelial cells lining internal organs such as the lung bronchus, where YAP/TAZ localize to the nucleus in proliferating basal layer stem cells but translocate to the cytoplasm in differentiated columnar cells.
Journal Current Opinion in Cell Biology
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Publisher website (DOI) 10.1016/j.ceb.2018.02.003
Europe PubMed Central 29477107
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