Conditional Deletion of AP-2β in the Periocular Mesenchyme of Mice Alters Corneal Epithelial Cell Fate and Stratification.
Conditional Deletion of AP-2β in the Periocular Mesenchyme of Mice Alters Corneal Epithelial Cell Fate and Stratification.
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DOI：
10.3390/ijms22168730
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发表时间：
2021-08-13
影响因子：
5.6
通讯作者：
West-Mays JA
中科院分区：
文献类型：
--
作者：
Walker H;Taiyab A;Deschamps P;Williams T;West-Mays JA
角膜是一种专门用于视觉的眼睛前部结构。角膜内皮和基质来源于眼周间充质(POM)，来源于神经脊细胞(NCCs)，复层角膜上皮来源于表面外胚层。活化蛋白-2β(AP-2β)在前膜中高表达，对前段发育起重要作用。利用AP-2β在NCC中有条件缺失的小鼠模型(AP-2βNCC KO)，我们研究了由此导致的角膜上皮异常。通过PAS和免疫组化染色，我们观察到与AP-2β缺失相关的上皮的结构和表型变化。除了突变的上皮未能复层外，我们还观察到分化上皮的标志物角蛋白-12缺失，角蛋白-15，角蛋白-15，边缘和结膜的标志物，扩展到中央上皮。转录因子PAX6和p63在野生型和突变型之间没有发现差异表达。然而，生长因子BMP4在突变的上皮中受到抑制。鉴于非NCC来源的上皮细胞，我们假设AP-2βNCC KO小鼠的异常是由于POM来源的间质调节信号的变化所致。我们的发现表明，基质通路，如Wnt/β-catenin信号通路可能调节BMP4的表达，从而影响细胞的命运和层积。
The cornea is an anterior eye structure specialized for vision. The corneal endothelium and stroma are derived from the periocular mesenchyme (POM), which originates from neural crest cells (NCCs), while the stratified corneal epithelium develops from the surface ectoderm. Activating protein-2β (AP-2β) is highly expressed in the POM and important for anterior segment development. Using a mouse model in which AP-2β is conditionally deleted in the NCCs (AP-2β NCC KO), we investigated resulting corneal epithelial abnormalities. Through PAS and IHC staining, we observed structural and phenotypic changes to the epithelium associated with AP-2β deletion. In addition to failure of the mutant epithelium to stratify, we also observed that Keratin-12, a marker of the differentiated epithelium, was absent, and Keratin-15, a limbal and conjunctival marker, was expanded across the central epithelium. Transcription factors PAX6 and P63 were not observed to be differentially expressed between WT and mutant. However, growth factor BMP4 was suppressed in the mutant epithelium. Given the non-NCC origin of the epithelium, we hypothesize that the abnormalities in the AP-2β NCC KO mouse result from changes to regulatory signaling from the POM-derived stroma. Our findings suggest that stromal pathways such as Wnt/β-Catenin signaling may regulate BMP4 expression, which influences cell fate and stratification.
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影响因子：
3.4
作者：
Lavker RM;Kaplan N;Wang J;Peng H
通讯作者：
Peng H
影响因子：
4.6
作者：
Li J;Xiao Y;Coursey TG;Chen X;Deng R;Lu F;Pflugfelder SC;Li DQ
通讯作者：
Li DQ
影响因子：
5.2
作者：
Di Girolamo, N.;Bobba, S.;Lyons, J. G.
通讯作者：
Lyons, J. G.
影响因子：
5.2
作者：
Chen, Z;De Paiva, CS;Li, DQ
通讯作者：
Li, DQ
DOI：
10.1002/dvdy.24141
发表时间：
2014-10
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Kerr CL;Zaveri MA;Robinson ML;Williams T;West-Mays JA
通讯作者：
West-Mays JA