Yap1 is required for maintenance of adult RPE differentiation
Open Access
- 29 March 2020
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 34 (5), 6757-6768
- https://doi.org/10.1096/fj.201903234r
Abstract
Nuclear YAP1 plays a critical role in regulation of stem cell proliferation, tissue regeneration, and organ size in many types of epithelia. Due to rapid turnover of most epithelial cell types, the cytoplasmic function of YAP1 in epithelial cells has not been well studied. The retinal pigment epithelium (RPE) is a highly polarized epithelial cell type maintained at a senescence state, and offers an ideal cell model to study the active role of YAP1 in maintenance of the adult epithelial phenotype. Here, we show that the cytoplasmic function of YAP1 is essential to maintain adult RPE differentiation. Knockout of Yap1 in the adult mouse RPE caused cell depolarization and tight junction breakdown, and led to inhibition of RPE65 expression, diminishment of RPE pigments, and retraction of microvilli and basal infoldings. These changes in RPE further prompted the loss of adjacent photoreceptor outer segments and photoreceptor death, which eventually led to decline of visual function in older mice between 6 and 12 months of age. Furthermore, nuclear β-catenin and its activity were significantly increased in mutant RPE. These results suggest that YAP1 plays an important role in active inhibition of Wnt/β-catenin signaling, and is essential for downregulation of β-catenin nuclear activity and prevention of dedifferentiation of adult RPE.Keywords
Funding Information
- National Eye Institute (EY027033)
This publication has 54 references indexed in Scilit:
- 14-3-3σ Regulates Keratinocyte Proliferation and Differentiation by Modulating Yap1 Cellular LocalizationJournal of Investigative Dermatology, 2015
- YAP/TAZ Incorporation in the β-Catenin Destruction Complex Orchestrates the Wnt ResponseCell, 2014
- The Hippo superhighway: signaling crossroads converging on the Hippo/Yap pathway in stem cells and developmentCurrent Opinion in Cell Biology, 2013
- Angiomotin-like Proteins Associate with and Negatively Regulate YAP1Online Journal of Public Health Informatics, 2011
- Hippo signaling at a glanceJournal of Cell Science, 2010
- The Hippo Signaling Pathway in Development and CancerDevelopmental Cell, 2010
- Zeb1 RepressesMitfand Regulates Pigment Synthesis, Cell Proliferation, and Epithelial MorphologyInvestigative Ophthalmology & Visual Science, 2009
- Elucidation of a Universal Size-Control Mechanism in Drosophila and MammalsCell, 2007
- A global double‐fluorescent Cre reporter mousegenesis, 2007
- The Retinal Pigment Epithelium in Visual FunctionPhysiological Reviews, 2005