Tian Natasha M, Pratt Thomas, Price David J
Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
Development. 2008 Dec;135(24):4081-9. doi: 10.1242/dev.023572. Epub 2008 Nov 12.
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.
哺乳动物的双眼视觉依赖于视网膜神经节细胞轴突在视交叉处的发散，其向对侧和同侧投射的数量受到严格控制。在小鼠中，对侧投射来自整个视网膜，而同侧投射来自颞腹侧视网膜。我们研究了对侧决定因子Foxg1如何调节这些投射模式的发育，Foxg1是一种叉头框转录因子，在鼻侧视网膜和视交叉处表达。在鼻侧视网膜中，Foxg1的缺失导致同侧投射数量增加以及同侧决定因子Zic2、Ephb1和Foxd1的异位表达，这表明鼻侧视网膜有能力表达一种通常被Foxg1抑制的同侧程序。通过将表达Foxg1的视网膜外植体和视交叉细胞与不表达Foxg1的视网膜外植体进行共培养，我们提供了功能证据，表明Foxg1通过在鼻侧视网膜中的作用促进对侧投射，并且在视交叉细胞中，Foxg1是产生一种迄今未被认识的支持视网膜神经节细胞轴突生长的活性所必需的。
