An essential role for frizzled 5 in mammalian ocular development
An essential role for frizzled 5 in mammalian ocular development
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DOI：
10.1242/dev.028076
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发表时间：
2008-11-01
期刊：
影响因子：
4.6
通讯作者：
Nathans, Jeremy
中科院分区：
文献类型：
--
作者：
Liu, Chunqiao;Nathans, Jeremy
小眼球、缺损和玻璃体腔内的持续性胎儿血管是人类最常见的先天性眼部异常，并且每一种都与多种遗传疾病相关。在这里，我们表明，在小鼠中，卷曲5（Fz 5）的损失-一个假定的Wnt受体表达在眼睛的领域，视杯和视网膜-导致所有这些缺陷与高反射率。在发育中的Fz 5（-/-）眼中，缺陷的顺序（按出现的顺序）是：腹侧视网膜中的细胞死亡增加、腹侧裂的延迟和/或不完全闭合、玻璃体腔中的间充质细胞过量、视网膜星形胶质细胞前体和成熟星形胶质细胞过量以及与大量色素细胞相关的玻璃体脉管系统的持续存在。Fz 5（-/-）小鼠在6月龄时也表现出迟发性进行性视网膜变性，这可能与成年视网膜中Muller胶质细胞中Fz 5的表达有关。这些结果表明，卷曲信号在哺乳动物眼睛发育中的核心作用，并可能与先天性人类眼部异常的病因有关。
Microphthalmia, coloboma and persistent fetal vasculature within the vitreous cavity are among the most common human congenital ocular anomalies, and each has been associated with a variety of genetic disorders. Here we show that, in the mouse, loss of frizzled 5 (Fz5) - a putative Wnt receptor expressed in the eye field, optic cup and retina - causes all of these defects with high penetrance. In the developing Fz5(-/-) eye, the sequence of defects, in order of appearance, is: increased cell death in the ventral retina, delayed and/or incomplete closure of the ventral fissure, an excess of mesenchymal cells in the vitreous cavity, an excess of retinal astrocyte precursors and mature astrocytes, and persistence of the hyaloid vasculature in association with a large number of pigment cells. Fz5(-/-) mice also exhibit a late-onset progressive retinal degeneration by similar to 6 months of age, which might be related to the expression of Fz5 in Muller glia in the adult retina. These results demonstrate a central role for frizzled signaling in mammalian eye development and are likely to be relevant to the etiology of congenital human ocular anomalies.