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Cited by 143Hippo pathway signaling and YAP/TAZRetinal Development and DisordersOcular Disorders and Treatments

Yap and Taz regulate retinal pigment epithelial cell fate

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Miesfeld, Joel B., Gestri, Gaia, Clark, Brian S., Flinn, Michael A., Poole, Richard J., Bader, Jason R., Besharse, Joseph C., Wilson, Stephen W. +1 more·2015·Development
DOI 10.1242/dev.119008PMC PMC4582179
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Abstract

During ocular morphogenesis the retinal pigment epithelium (RPE) and neural retina segregate fates from a bi-potential progenitor pool of cells comprising the optic vesicle. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. In support, a Tead responsive transgene expresses within the domain of the optic cup from which RPE arises and Yap immunoreactivity localizes to nuclei of prospective RPE cells. yap mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz mutant alleles such that when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap dependent RPE cell-type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosage-dependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson's chorioretinal atrophy and congenital retinal coloboma.

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  • Injection of a Tol2 transposon-based plasmid containing tfec promoter driving full-length tfec rescues the iridophore phenotype in tfec mutants.

    “The iridophore phenotype could be successfully rescued via injection of a Tol2 transposon-based plasmid containing 2.4 kb of the tfec promoter [42], guiding tissue-specific expression of full-length tfec (Fig 3G–3K).”

    From The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor (2021) · cites this paper as [42]

    The Materials and Methods section (Generation of plasmids and transgenic lines; page unavailable) describes a Tol2 construct using a 2.7 kb tfec promoter to drive eGFP, supporting the citation's use as a precedent for a tfec-promoter construct. It does not describe the cited 2.4 kb promoter. The rescue experiment appears to be the citing authors’ own result, not a result attributed to this source. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Miesfeld, J. B., Gestri, G., Clark, B. S., Flinn, M. A., Poole, R. J., Bader, J. R., Besharse, J. C., Wilson, S. W., & Link, B. A.
Affiliations
  • Medical College of Wisconsin (US)
  • University College London (GB)
Corresponding author
Link, Brian A.
ORCID
Venue
Development
Publisher
The Company of Biologists
Published
2015-01-01
Volume
142
Issue
17
Pages
3021-32
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.119008
PMC
PMC4582179
OpenAlex
W2107449497
Cited by
143
References
2
Citations by year
2026: 8 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 19 · 2020: 16 · 2019: 23 · 2018: 18 · 2017: 14 · 2016: 3 · 2015: 2
FWCI
5.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Development (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion, cc-by)
Funders
  • Wellcome Trust
  • Medical Research Council (MR/L003775/1)
  • National Heart, Lung, and Blood Institute (F32HL150958)
  • National Eye Institute (T32EY014536, P30EY001931, R01EY003222, R01EY014167, T32EY014537, P30EY008126)
  • National Cancer Institute (P30CA068485)
  • National Center for Research Resources (G20RR030956)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Ocular Disorders and Treatments
Keywords
YAP, TAZ, TEAD transcription factors, retinal pigment epithelium, ocular morphogenesis, zebrafish, coloboma, transcriptional cofactors
MeSH terms
YAP-Signaling Proteins, TEA Domain Transcription Factors, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Alleles, Animals, Cell Nucleus, Coloboma, DNA-Binding Proteins, Epithelial Cells, Humans, Morphogenesis, Mutation, Nuclear Proteins, Phenotype, Protein Binding, RNA, Messenger, Transcription Factors, Zebrafish, Signal Transduction, Trans-Activators, Up-Regulation, Apoptosis, Genes, Reporter, Gene Expression Regulation, Developmental, Cell Lineage, Transgenes, Zebrafish Proteins, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Retinal Pigment Epithelium, HEK293 Cells

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