Zic2 patterns binocular vision by specifying the uncrossed retinal projection

Zic2 patterns binocular vision by specifying the uncrossed retinal projection
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DOI:
10.1016/s0092-8674(03)00684-6
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发表时间:
2003-09-05
期刊:
影响因子:
64.5
通讯作者:
Mason, CA
Mason, CA
中科院分区:
生物学1区
文献类型:
--
作者:
Herrera, E;Brown, L;Mason, CA

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在中枢神经系统发育过程中,转录因子的组合表达控制神经元亚型的身份和随后的轴突轨迹。还没有鉴定出将视交叉处的视网膜神经节细胞(RGC)轴突路由到适当半球的调节基因,这是正确双眼视觉的关键模式。在这里,我们表明,锌指转录因子Zic 2,一个脊椎动物同源的果蝇基因奇配对,在RGCs中表达的一个不交叉的轨迹期间,这个亚群从腹颞视网膜向视交叉增长。损失和增益的功能分析表明,Zic2是必要的,足以调节RGC轴突排斥线索在视交叉中线。此外,Zic 2的表达反映了不同物种的双目性程度,表明Zic 2是同侧投射的RGC的进化保守决定因素。这些数据为轴突在中线寻路的转录编码提供了证据。
During CNS development, combinatorial expression of transcription factors controls neuronal subtype identity and subsequent axonal trajectory. Regulatory genes designating the routing of retinal ganglion cell (RGC) axons at the optic chiasm to the appropriate hemisphere, a pattern critical for proper binocular vision, have not been identified. Here, we show that the zinc finger transcription factor Zic2, a vertebrate homolog of the Drosophila gene odd-paired, is expressed in RGCs with an uncrossed trajectory during the period when this subpopulation grows from the ventrotemporal retina toward the optic chiasm. Loss-and gain-of-function analyses indicate that Zic2 is necessary and sufficient to regulate RGC axon repulsion by cues at the optic chiasm midline. Moreover, Zic2 expression reflects the extent of binocularity in different species, suggesting that Zic2 is an evolutionarily conserved determinant of RGCs that project ipsilaterally. These data provide evidence for transcriptional coding of axon pathfinding at the midline.