Nejvíce citovaný článek - PubMed ID 11943482
Complex regulatory element within the gammaE- and gammaF-crystallin enhancers mediates Pax6 regulation and is required for induction by retinoic acid
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.
- MeSH
- beta-katenin genetika metabolismus MeSH
- buněčná diferenciace genetika MeSH
- buněčný cyklus genetika MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- epitelové buňky metabolismus MeSH
- katarakta genetika metabolismus MeSH
- krystaliny genetika metabolismus MeSH
- lidé MeSH
- mikroftalmie genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- myši transgenní genetika metabolismus MeSH
- myši MeSH
- oční čočka metabolismus MeSH
- promotorové oblasti (genetika) genetika MeSH
- signální dráha Wnt genetika MeSH
- signální transdukce genetika MeSH
- transkripční faktor LEF-1 MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-katenin MeSH
- DNA vazebné proteiny MeSH
- krystaliny MeSH
- Lef1 protein, mouse MeSH Prohlížeč
- transkripční faktor LEF-1 MeSH
