University of Edinburgh, Centre for Integrative Physiology, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
Dev Biol. 2013 Aug 15;380(2):299-313. doi: 10.1016/j.ydbio.2013.04.017. Epub 2013 Apr 24.
The ciliary margin (CM) develops in the peripheral retina and gives rise to the iris and the ciliary body. The Wnt/β-catenin signalling pathway has been implicated in ciliary margin development. Here, we tested the hypothesis that in the developing mouse retina Foxg1 is responsible for suppressing the Wnt/β-catenin pathway and restricting CM development. We showed that there is excess CM tissue in Foxg1(-/-) null embryos and this expansion is more pronounced in the nasal retina where Foxg1 normally shows its highest expression levels. Results on expression of a reporter allele for Wnt/β-catenin signalling and of Lef1, a target of Wnt/β-catenin signalling, displayed significant upregulation of this pathway in Foxg1(-/-) nulls at embryonic days 12.5 and 14.5. Interestingly, this upregulation was observed specifically in the nasal retina, where normally very few Wnt-responsive cells are observed. These results indicate a suppressive role of Foxg1 on this signalling pathway. Our results reveal a new role of Foxg1 in limiting CM development in the nasal peripheral retina and add a new molecular player in the developmental network involved in CM specification.
纤毛缘（CM）在周边视网膜中发育，并产生虹膜和睫状体。Wnt/β-catenin 信号通路与纤毛缘发育有关。在这里，我们测试了以下假设：在发育中的小鼠视网膜中，Foxg1 负责抑制 Wnt/β-catenin 通路并限制 CM 发育。我们发现 Foxg1(-/-) 缺失胚胎中存在过多的 CM 组织，而在正常情况下 Foxg1 表达水平最高的鼻侧视网膜中，这种扩张更为明显。Wnt/β-catenin 信号的报告基因等位基因和 Lef1（Wnt/β-catenin 信号的靶标）的表达结果显示，在 E12.5 和 E14.5 的 Foxg1(-/-) 缺失胚胎中，该通路的表达显著上调。有趣的是，这种上调仅在鼻侧视网膜中观察到，在正常情况下，很少观察到对 Wnt 有反应的细胞。这些结果表明 Foxg1 对该信号通路具有抑制作用。我们的结果揭示了 Foxg1 在限制鼻侧周边视网膜 CM 发育中的新作用，并为参与 CM 特化的发育网络增加了一个新的分子参与者。
