Liu Chunqiao, Nathans Jeremy
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Development. 2008 Nov;135(21):3567-76. doi: 10.1242/dev.028076. Epub 2008 Oct 2.
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 approximately 6 months of age, which might be related to the expression of Fz5 in Müller 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.
小眼症、脉络膜缺损和玻璃体腔内永存原始玻璃体血管系统是人类最常见的先天性眼部异常，且每种异常都与多种遗传疾病相关。我们在此表明，在小鼠中，卷曲蛋白5（Fz5）缺失——一种在眼原基、视杯和视网膜中表达的假定Wnt受体——会导致所有这些缺陷，且具有高外显率。在发育中的Fz5（-/-）眼中，缺陷出现的顺序依次为：视网膜腹侧细胞死亡增加、腹侧裂闭合延迟和/或不完全、玻璃体腔内间充质细胞过多、视网膜星形胶质细胞前体和成熟星形胶质细胞过多，以及与大量色素细胞相关的玻璃体血管系统持续存在。Fz5（-/-）小鼠在约6月龄时还表现出迟发性进行性视网膜变性，这可能与成年视网膜中Müller胶质细胞中Fz5的表达有关。这些结果证明了卷曲蛋白信号在哺乳动物眼睛发育中的核心作用，并且可能与人类先天性眼部异常的病因相关。
