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首页> 外文期刊>Development >Semaphorin 3d guides laterality of retinal ganglion cell projections in zebrafish.
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Semaphorin 3d guides laterality of retinal ganglion cell projections in zebrafish.

机译:Semaphorin 3d引导斑马鱼中视网膜神经节细胞投射的侧向性。

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摘要

The optic chiasm is an important choice point at which retinal ganglion cell (RGC) axons either cross the midline to innervate the contralateral brain or turn back to innervate the ipsilateral brain. Guidance cues that regulate this decision, particularly those directing the midline crossing of contralateral axons, are still not well understood. Here we show that Sema3d, a secreted semaphorin expressed at the midline, guides the crossing of RGC axons in zebrafish. Both Sema3d knockdown and ubiquitous overexpression induced aberrant ipsilateral projections, suggesting that Sema3d normally guides axons into the contralateral optic tract. Live imaging in vivo showed that RGC growth cones responded to ubiquitous Sema3d overexpression by pausing for extended periods and increasing their exploratory behavior at the midline, suggesting that Sema3d overexpression causes the midline environment to become less favorable for RGC axon extension. Interestingly, Sema3d overexpression did not affect growth cone behaviors before the midline, suggesting that RGC axons normally respond to Sema3d only upon reaching the midline. After Sema3d knockdown, growth cones grew across the midline but then paused or repeatedly retracted, impairing their ability to leave the midline region. Our results indicate that a proper balance of Sema3d is needed at the midline for the progression of RGC axons from the chiasm midline into the contralateral optic tract.
机译:视神经混乱是视网膜神经节细胞(RGC)轴突穿过中线以支配对侧大脑或转回以支配同侧大脑的重要选择点。仍然没有很好地理解调节这一决定的指导线索,特别是那些指导对侧轴突中线交叉的指导线索。在这里,我们显示Sema3d,一种在中线表达的分泌信号量,指导斑马鱼中RGC轴突的穿越。 Sema3d的敲低和普遍存在的过表达均引起同侧异常畸形,这表明Sema3d通常将轴突引导到对侧视神经束中。体内实时成像显示,RGC生长锥通过延长暂停时间和增加其在中线的探索行为来响应普遍存在的Sema3d过表达,这表明Sema3d过表达会导致中线环境对RGC轴突延伸变得不利。有趣的是,Sema3d的过表达不会影响中线之前的生长锥行为,这表明RGC轴突通常仅在到达中线时才对Sema3d做出反应。在Sema3d击倒后,生长锥穿过中线生长,但随后暂停或反复缩回,从而削弱了它们离开中线区域的能力。我们的结果表明,中线需要Sema3d的适当平衡,以使RGC轴突从chi部中线发展到对侧视神经束。

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