Hsieh Yi-Wen, Zhang Xiang-Mei, Lin Eddie, Oliver Guillermo, Yang Xian-Jie
Department of Ophthalmology, Jules Stein Eye Institute, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Dev Biol. 2002 Aug 15;248(2):265-80. doi: 10.1006/dbio.2002.0732.
The anterior segment of the vertebrate eye consists of highly organized and specialized ocular tissues critical for normal vision. The periocular mesenchyme, originating from the neural crest, contributes extensively to the anterior segment. During chick eye morphogenesis, the homeobox gene Six3 is expressed in a subset of periocular mesenchymal cells and in differentiating anterior segment tissues. Retrovirus-mediated misexpression of Six3 causes eye anterior segment malformation, including corneal protrusion and opacification, ciliary body and iris hypoplasia, and trabecular meshwork dysgenesis. Histological and molecular marker analyses demonstrate that Six3 misexpression disrupts the integrity of the corneal endothelium and the expression of extracellular matrix components critical for corneal transparency. Six3 misexpression also leads to a reduction of the periocular mesenchymal cell population expressing Lmx1b, Pitx2, and Pax6, transcription factors critical for eye anterior segment morphogenesis. Moreover, elevated levels of Six3 attenuate proliferation of periocular mesenchymal cells in vitro and differentiating anterior segment tissues in vivo. These results suggest that, in addition to its function in eye primordium determination, Six3 plays a role in regulating the development of the vertebrate eye anterior segment.
脊椎动物眼睛的前段由对正常视觉至关重要的高度组织化和特化的眼组织组成。眼周间充质起源于神经嵴，对前段的形成有广泛贡献。在鸡胚眼形态发生过程中，同源框基因Six3在眼周间充质细胞的一个亚群以及正在分化的前段组织中表达。逆转录病毒介导的Six3错误表达会导致眼前段畸形，包括角膜突出和混浊、睫状体和虹膜发育不全以及小梁网发育异常。组织学和分子标记分析表明，Six3错误表达会破坏角膜内皮的完整性以及对角膜透明度至关重要的细胞外基质成分的表达。Six3错误表达还会导致表达Lmx1b、Pitx2和Pax6的眼周间充质细胞数量减少，这些转录因子对眼前段形态发生至关重要。此外，Six3水平升高会减弱眼周间充质细胞在体外的增殖以及体内正在分化的前段组织的增殖。这些结果表明，Six3除了在眼原基确定中发挥作用外，还在调节脊椎动物眼前段的发育中起作用。
