Karlstrom R O, Trowe T, Klostermann S, Baier H, Brand M, Crawford A D, Grunewald B, Haffter P, Hoffmann H, Meyer S U, Müller B K, Richter S, van Eeden F J, Nüsslein-Volhard C, Bonhoeffer F
Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany.
Development. 1996 Dec;123:427-38. doi: 10.1242/dev.123.1.427.
We have isolated mutants in the zebrafish Danio rerio that have defects in axonal connectivity between the retina and tectum. 5-day-old fish larvae were screened by labeling retinal ganglion cells with DiI and DiO and observing their axonal projections to and on the tectum. 82 mutations, representing 13 complementation groups and 6 single allele loci, were found that have defects in retinal ganglion cell axon pathfinding to the tectum. These pathfinding genes fall into five classes, based on the location of pathfinding errors between eye and tectum. In Class I mutant larvae (belladonna, detour, you-too, iguana, umleitung, blowout) axons grow directly to the ipsilateral tectal lobe after leaving the eye. Class II mutant larvae (chameleon, bashful) have ipsilaterally projecting axons and, in addition, pathfinding mistakes are seen within the eye. In Class III mutant larvae (esrom, tilsit, tofu) fewer axons than normal cross the midline, but some axons do reach the contralateral tectal lobe. Class IV mutant larvae (boxer, dackel, pinscher) have defects in axon sorting after the midline and retinal axons occasionally make further pathfinding errors upon reaching the contralateral tectal lobe. Finally, Class V mutant larvae (bashful, grumpy, sleepy, cyclops, astray) have anterior-posterior axon trajectory defects at or after the midline. The analysis of these mutants supports several conclusions about the mechanisms of retinal axon pathfinding from eye to tectum. A series of sequential cues seems to guide retinal axons to the contralateral tectal lobe. Pre-existing axon tracts seem not to be necessary to guide axons across the midline. The midline itself seems to play a central role in guiding retinal axons. Axons in nearby regions of the brain seem to use different cues to cross the ventral midline. Mutant effects are not all-or-none, as misrouted axons may reach their target, and if they do, they project normally on the tectum. The retinotectal pathfinding mutants reveal important choice points encountered by neuronal growth cones as they navigate between eye and tectum.
我们在斑马鱼（Danio rerio）中分离出了一些突变体，这些突变体在视网膜与视顶盖之间的轴突连接方面存在缺陷。通过用DiI和DiO标记视网膜神经节细胞，并观察它们在视顶盖上的轴突投射，对5天大的鱼幼虫进行了筛选。发现了82个突变，这些突变代表13个互补群和6个单等位基因位点，它们在视网膜神经节细胞轴突向视顶盖的寻路过程中存在缺陷。根据眼与视顶盖之间寻路错误的位置，这些寻路基因可分为五类。在I类突变幼虫（颠茄、绕行、你也一样、鬣蜥、改道、爆裂）中，轴突离开眼睛后直接生长到同侧视叶。II类突变幼虫（变色龙、害羞）有同侧投射的轴突，此外，在眼睛内部也能看到寻路错误。在III类突变幼虫（埃斯罗姆、蒂尔西特、豆腐）中，穿过中线的轴突比正常情况少，但仍有一些轴突能到达对侧视叶。IV类突变幼虫（拳击手、腊肠犬、平斯彻）在中线后的轴突分选方面存在缺陷，视网膜轴突在到达对侧视叶时偶尔会出现进一步的寻路错误。最后，V类突变幼虫（害羞、脾气暴躁、困倦、独眼、迷路）在中线处或中线后存在前后轴突轨迹缺陷。对这些突变体的分析支持了关于视网膜轴突从眼睛到视顶盖寻路机制的几个结论。一系列连续的线索似乎引导视网膜轴突到达对侧视叶。预先存在的轴突束似乎不是引导轴突穿过中线所必需的。中线本身似乎在引导视网膜轴突方面起着核心作用。大脑附近区域的轴突似乎使用不同的线索穿过腹侧中线。突变效应并非全有或全无，因为走错路的轴突可能会到达其目标，并且如果到达了，它们会在视顶盖上正常投射。视网膜-视顶盖寻路突变体揭示了神经元生长锥在眼睛和视顶盖之间导航时遇到的重要选择点。
