Ocular lens morphogenesis is a model for investigating mechanisms of cellular differentiation, spatial and temporal gene expression control, and chromatin regulation. Brg1 (Smarca4) and Snf2h (Smarca5) are catalytic subunits of distinct ATP-dependent chromatin remodeling complexes implicated in transcriptional regulation. Previous studies have shown that Brg1 regulates both lens fiber cell differentiation and organized degradation of their nuclei (denucleation). Here, we employed a conditional Snf2h(flox) mouse model to probe the cellular and molecular mechanisms of lens formation. Depletion of Snf2h induces premature and expanded differentiation of lens precursor cells forming the lens vesicle, implicating Snf2h as a key regulator of lens vesicle polarity through spatial control of Prox1, Jag1, p27(Kip1) (Cdkn1b) and p57(Kip2) (Cdkn1c) gene expression. The abnormal Snf2h(-/-) fiber cells also retain their nuclei. RNA profiling of Snf2h(-/) (-) and Brg1(-/-) eyes revealed differences in multiple transcripts, including prominent downregulation of those encoding Hsf4 and DNase IIβ, which are implicated in the denucleation process. In summary, our data suggest that Snf2h is essential for the establishment of lens vesicle polarity, partitioning of prospective lens epithelial and fiber cell compartments, lens fiber cell differentiation, and lens fiber cell nuclear degradation.
- MeSH
- adenosintrifosfatasy metabolismus MeSH
- autofagie MeSH
- biologické modely MeSH
- buněčná diferenciace * MeSH
- buněčné jádro metabolismus MeSH
- buněčný cyklus MeSH
- chromozomální proteiny, nehistonové metabolismus MeSH
- DNA vazebné proteiny metabolismus MeSH
- DNA-helikasy metabolismus MeSH
- embryo savčí metabolismus MeSH
- epitelové buňky cytologie metabolismus MeSH
- jaderné proteiny metabolismus MeSH
- kompartmentace buňky MeSH
- mitofagie MeSH
- mutace genetika MeSH
- myši knockoutované MeSH
- oční čočka cytologie embryologie MeSH
- restrukturace chromatinu * MeSH
- transkripční faktor PAX6 metabolismus MeSH
- transkripční faktory metabolismus MeSH
- transkriptom genetika MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
