Semaphorin 3d guides laterality of retinal ganglion cell projections in zebrafish
Semaphorin 3d guides laterality of retinal ganglion cell projections in zebrafish
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DOI：
10.1242/dev.02272
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发表时间：
2006-03-15
期刊：
影响因子：
4.6
通讯作者：
Halloran, MC
中科院分区：
文献类型：
--
作者：
Sakai, JA;Halloran, MC
视交叉是视网膜神经节细胞（RGC）轴突穿过中线支配对侧脑或返回支配同侧脑的重要选择点。调控这一决定的引导线索，特别是那些引导对侧轴突中线交叉的线索，仍然没有得到很好的理解。本研究表明，在斑马鱼中线表达的分泌信号蛋白Sema3d引导RGC轴突的交叉。Sema3d敲低和普遍过表达都会引起同侧异常投射，这表明Sema3d通常引导轴突进入对侧视束。活体成像显示，RGC生长锥对普遍存在的Sema3d过表达做出反应，暂停时间延长，并增加其在中线的探索行为，这表明Sema3d过表达导致中线环境对RGC轴突延伸变得不那么有利。有趣的是，Sema3d过表达并不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有反应。Sema3d敲除后，生长球果在中线生长，但随后暂停或反复缩回，损害了它们离开中线区域的能力。我们的研究结果表明，RGC轴突从交叉中线进入对侧视束需要在中线处保持适当的Sema3d平衡。
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.