Foxg1 is required to limit the formation of ciliary margin tissue and Wnt/β-catenin signalling in the developing nasal retina of the mouse.
Foxg1 is required to limit the formation of ciliary margin tissue and Wnt/β-catenin signalling in the developing nasal retina of the mouse.
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DOI：
10.1016/j.ydbio.2013.04.017
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发表时间：
2013-08-15
影响因子：
2.7
通讯作者：
Price, David J.
中科院分区：
文献类型：
--
作者：
Fotaki, Vassiliki;Smith, Rowena;Pratt, Thomas;Price, David J.
睫状体缘（ciliary margin， CM）在视网膜周围发育，并产生虹膜和睫状体。Wnt/β-catenin信号通路与纤毛边缘发育有关。在这里，我们验证了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发育的假设。我们发现Foxg1−/−缺失胚胎中存在过量的CM组织，这种扩张在鼻视网膜中更为明显，而鼻视网膜通常是Foxg1表达水平最高的地方。结果显示，Wnt/β-catenin信号通路的报告等位基因和Wnt/β-catenin信号通路的靶基因Lef1的表达在胚胎12.5和14.5天时在Foxg1−/−nuls中显著上调。有趣的是，这种上调是在鼻视网膜中特别观察到的，在那里通常很少观察到wnt反应细胞。这些结果表明Foxg1在这一信号通路上具有抑制作用。我们的研究结果揭示了Foxg1在限制鼻外周视网膜CM发育中的新作用，并在涉及CM规范的发育网络中添加了一个新的分子参与者。Foxg1在发育中的视网膜中以鼻高到颞低的梯度表达。在Foxg1−/−突变的视网膜中观察到睫状缘扩张。Wnt/β-catenin信号在Foxg1−/−外周视网膜中上调。Foxg1在控制纤毛边缘发育中的新作用被提出。
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. Foxg1 is expressed in a nasal-high to temporal-low gradient in developing retina. Ciliary margin expansion is observed nasally in the Foxg1−/− mutant retina. Wnt/β-catenin signalling is upregulated in the Foxg1−/− peripheral retina nasally. A new role of Foxg1 in controlling ciliary margin development is proposed.
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影响因子：
5.3
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