PloS one, 2013-10, Vol.8 (10), p.e78279-e78279
2013
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- Autor(en) / Beteiligte
- Titel
- Ectopic activation of Wnt/β-catenin signaling in lens fiber cells results in cataract formation and aberrant fiber cell differentiation
- Ist Teil von
- PloS one, 2013-10, Vol.8 (10), p.e78279-e78279
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The Wnt/β-catenin signaling pathway controls many processes during development, including cell proliferation, cell differentiation and tissue homeostasis, and its aberrant regulation has been linked to various pathologies. In this study we investigated the effect of ectopic activation of Wnt/β-catenin signaling during lens fiber cell differentiation. To activate Wnt/β-catenin signaling in lens fiber cells, the transgenic mouse referred to as αA-CLEF was generated, in which the transactivation domain of β-catenin was fused to the DNA-binding protein LEF1, and expression of the transgene was controlled by αA-crystallin promoter. Constitutive activation of Wnt/β-catenin signaling in lens fiber cells of αA-CLEF mice resulted in abnormal and delayed fiber cell differentiation. Moreover, adult αA-CLEF mice developed cataract, microphthalmia and manifested downregulated levels of γ-crystallins in lenses. We provide evidence of aberrant expression of cell cycle regulators in embryonic lenses of αA-CLEF transgenic mice resulting in the delay in cell cycle exit and in the shift of fiber cell differentiation to the central fiber cell compartment. Our results indicate that precise regulation of the Wnt/β-catenin signaling activity during later stages of lens development is essential for proper lens fiber cell differentiation and lens transparency.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0078279Titel-ID: cdi_plos_journals_1447630423
- Format
- –
- Schlagworte
- Aberration, Activation, Animals, beta Catenin - genetics, beta Catenin - metabolism, Cataract - genetics, Cataract - metabolism, Cataracts, Cell adhesion & migration, Cell cycle, Cell Cycle - genetics, Cell differentiation, Cell Differentiation - genetics, Cell proliferation, Control, Crystal structure, Crystallin, Crystallinity, Crystallins - genetics, Crystallins - metabolism, Cyclin-dependent kinases, Deoxyribonucleic acid, Developmental stages, Differentiation (biology), DNA, DNA-binding protein, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Embryos, Epithelial Cells - metabolism, Gene expression, Gene Expression Regulation, Developmental, Genes, Genetics, Genotype & phenotype, Growth factors, Homeostasis, Humans, Kinases, Lens, Crystalline - metabolism, Lenses, Ligands, Lymphoid Enhancer-Binding Factor 1, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic - genetics, Mice, Transgenic - metabolism, Microphthalmia, Microphthalmos - genetics, Microphthalmos - metabolism, Mutation, Promoter Regions, Genetic - genetics, Proteins, Regulators, Signal transduction, Signal Transduction - genetics, Signaling, Transcription factors, Transgenic mice, Transparency, Wnt protein, Wnt Signaling Pathway - genetics, β-Catenin