Foxg1 regulates retinal axon pathfinding by repressing an ipsilateral program in nasal retina and by causing optic chiasm cells to exert a net axonal growth-promoting activity
Foxg1 regulates retinal axon pathfinding by repressing an ipsilateral program in nasal retina and by causing optic chiasm cells to exert a net axonal growth-promoting activity
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DOI：
10.1242/dev.023572
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发表时间：
2008-12-15
期刊：
影响因子：
4.6
通讯作者：
Price, David J.
中科院分区：
文献类型：
--
作者：
Tian, Natasha M.;Pratt, Thomas;Price, David J.
哺乳动物的双眼视觉依赖于视交叉处视网膜神经节细胞轴突的分化，其数量严格控制在对侧和同侧。在小鼠中，对侧突起来自整个视网膜，而同侧突起来自腹颞视网膜。我们研究了这些凸出模式的发展如何受到对侧决定因子Foxg1的调控，Foxg1是在鼻视网膜和交叉处表达的叉头盒转录因子。在鼻视网膜中，Foxg1的缺失导致同侧突起数量的增加和同侧决定因子Zic2、Ephb1和Foxd1的异位表达，这表明鼻视网膜能够表达通常被Foxg1抑制的同侧程序。通过将表达Foxg1的视网膜外植体与Foxg1缺失的视网膜外植体和交叉细胞联合培养，我们提供了功能证据，证明Foxg1通过在鼻视网膜中的作用促进对侧投射，并且在交叉细胞中，Foxg1是产生迄今未被识别的支持RGC轴突生长的活性所必需的。
Mammalian binocular vision relies on the divergence of retinal ganglion cell axons at the optic chiasm, with strictly controlled numbers projecting contralaterally and ipsilaterally. In mouse, contralateral projections arise from the entire retina, whereas ipsilateral projections arise from ventrotemporal retina. We investigate how development of these patterns of projection is regulated by the contralateral determinant Foxg1, a forkhead box transcription factor expressed in nasal retina and at the chiasm. In nasal retina, loss of Foxg1 causes increased numbers of ipsilateral projections and ectopic expression of the ipsilateral determinants Zic2, Ephb1 and Foxd1, indicating that nasal retina is competent to express an ipsilateral program that is normally suppressed by Foxg1. Using co-cultures that combine Foxg1-expressing with Foxg1-null retinal explants and chiasm cells, we provide functional evidence that Foxg1 promotes contralateral projections through actions in nasal retina, and that in chiasm cells, Foxg1 is required for the generation of a hitherto unrecognized activity supporting RGC axon growth.