Zic2 regulates retinal ganglion cell axon avoidance of ephrinB2 through inducing expression of the guidance receptor EphB1
Zic2 regulates retinal ganglion cell axon avoidance of ephrinB2 through inducing expression of the guidance receptor EphB1
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DOI：
10.1523/jneurosci.0632-08.2008
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发表时间：
2008-06-04
影响因子：
5.3
通讯作者：
Mason, Carol A.
中科院分区：
文献类型：
--
作者：
Lee, Ramee;Petros, Timothy J.;Mason, Carol A.
视网膜轴突到大脑中同侧和对侧目标的导航取决于在视交叉处穿过或避开中线的决定，这是建立双眼视觉通路的关键引导动作。先前的工作已经鉴定了特异性引导受体EphB 1，其介导未交叉的轴突在视交叉中线处远离其配体ephrinB 2的排斥（威廉姆斯等人，2003）和转录因子Zic 2，其与EphB 1一样，是形成同侧视网膜投影所需的（Herrera et al.，2003年）。尽管报道的定位相似性暗示Zic 2调节EphB 1（Herrera et al.，2003;威廉姆斯等人，2003; Pak等人，2004），Zic 2是否驱动EphB 1蛋白的表达尚未阐明。在这里，我们表明，EphB 1蛋白表达在轴突的生长锥从ventrotemporal（VT）视网膜，项目同侧和eprinB 2的排斥是由生长锥上存在这种受体决定的。此外，Zic 2异位递送到来自非VT视网膜的外植体中诱导EphB 1 mRNA和蛋白的表达。上调的EphB 1受体蛋白定位于生长锥，并且是功能性的，因为它足以改变视网膜神经节细胞轴突行为，从延伸到ephrinB 2底物上，到避开ephrinB 2底物。我们的研究结果表明，Zic 2上调EphB 1的表达，并定义了一个转录因子和表达的指导受体蛋白在脊椎动物中线轴突指导所必需的链接。
The navigation of retinal axons to ipsilateral and contralateral targets in the brain depends on the decision to cross or avoid the midline at the optic chiasm, a critical guidance maneuver that establishes the binocular visual pathway. Previous work has identified a specific guidance receptor, EphB1, that mediates the repulsion of uncrossed axons away from its ligand, ephrinB2, at the optic chiasm midline (Williams et al., 2003), and a transcription factor Zic2, that, like EphB1, is required for formation of the ipsilateral retinal projection (Herrera et al., 2003). Although the reported similarities in localization implicated that Zic2 regulates EphB1 (Herrera et al., 2003; Williams et al., 2003; Pak et al., 2004), whether Zic2 drives expression of EphB1 protein has not been elucidated. Here we show that EphB1 protein is expressed in the growth cones of axons from ventrotemporal (VT) retina that project ipsilaterally and that repulsion by ephrinB2 is determined by the presence of this receptor on growth cones. Moreover, ectopic delivery of Zic2 into explants from non-VT retina induces expression of EphB1 mRNA and protein. The upregulated EphB1 receptor protein is localized to growth cones and is functional, because it is sufficient to change retinal ganglion cell axon behavior from extension onto, to avoidance of, ephrinB2 substrates. Our results demonstrate that Zic2 upregulates EphB1 expression and define a link between a transcription factor and expression of a guidance receptor protein essential for axon guidance at the vertebrate midline.