Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development.
Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development.
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视网膜发育对眼表外胚层 Smad4 的需求
DOI：
10.1371/journal.pone.0159639
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Li J;Wang S;Anderson C;Zhao F;Qin Y;Wu D;Wu X;Liu J;He X;Zhao J;Zhang J
小眼症的特点是眼睛异常小，通常是视网膜发育不良，占儿童失明的11%。目前还没有有效的治疗方法，其潜在的机制，特别是视网膜发育不良是如何从小眼症发展而来的，以及它是否依赖于晶状体外胚层的信号，仍然不清楚。TGF-β超家族基因突变已在小眼症患者中被发现。使用条件敲除小鼠，我们解决了眼表外胚层衍生的Smad4是否调节视网膜发育的问题。我们发现Smad4在晶状体表面外胚层的特异性缺失会导致小眼症和视网膜发育不良。基因敲除小鼠视网膜发育不良是由视网膜细胞分化延迟或失败和凋亡引起的。微阵列分析显示，敲除视网膜中Hedgehog和Wnt信号通路的成员受到影响，这表明眼表外胚层来源的Smad4可以调节视网膜中的Hedgehog和Wnt信号通路。我们的研究提示眼表外胚层缺损可能影响视网膜发育。
Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal development.