Robos are required for the correct targeting of retinal ganglion cell axons in the visual pathway of the brain

Robos are required for the correct targeting of retinal ganglion cell axons in the visual pathway of the brain
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DOI:
10.1016/j.mcn.2007.12.017
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发表时间:
2008-04-01
影响因子:
3.5
通讯作者:
Sundaresan, Vasi
Sundaresan, Vasi
中科院分区:
医学3区
文献类型:
--
作者:
Plachez, Celine;Andrews, William;Sundaresan, Vasi

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从视网膜到大脑的轴突投射受包括Slit家族配体的分子调节[Thompson,H.,Barker,D.,Camand,O.,埃尔斯金,L.,2006年a。裂隙有助于哺乳动物视束中视网膜神经节细胞轴突的引导。Dev. 296,476-484,Thompson,H.,Camand,O.,Barker,D.,埃尔斯金,L.,2006年b。Slit蛋白调节背侧和腹侧视网膜内视网膜神经节细胞轴突引导的不同方面。神经科学杂志26,8082-8091]。然而,哺乳动物(称为Robos)中Slit受体在视觉系统发育中的作用尚未研究。在这里,我们检查了Robo 1和2突变小鼠,发现Robos调节视网膜神经节细胞(RGC)轴突沿着整个视觉投射的正确靶向。我们注意到RGC轴突异常投射到大脑皮层,这是一个通常不被RGC轴突靶向的区域。视交叉沿着喙尾轴扩展(类似于Slit突变小鼠,Plump,A.S.,埃尔斯金,L.,Sabatier,C.,Brose,K.,Epstein,C.J.,古德曼,C.S.,梅森,CA,Tessier-Lavigne,M.,2002. Slit 1和Slit 2合作防止小鼠视觉系统中视网膜轴突的过早中线交叉。Neuron 33,219-232),具有异位交叉点,并且一些轴突向皮质脊髓束尾部突出。此外,我们发现轴突旺盛地投射到间脑。这些缺陷在Robo 2中比Robot敲除动物更明显,暗示Robo 2是视觉系统发育中的主要Robo受体。(c)2007年爱思唯尔公司All rights reserved.
Axonal projections from the retina to the brain are regulated by molecules including the Slit family of ligands [Thompson, H., Barker, D., Camand, O., Erskine, L., 2006a. Slits contribute to the guidance of retinal ganglion cell axons in the mammalian optic tract. Dev. Biol. 296, 476-484, Thompson, H., Camand, O., Barker, D., Erskine, L., 2006b. Slit proteins regulate distinct aspects of retinal ganglion cell axon guidance within dorsal and ventral retina. J. Neurosci. 26, 8082-8091]. However, the roles of Slit receptors in mammals, (termed Robos), have not been investigated in visual system development. Here we examined Robo1 and 2 mutant mice and found that Robos regulate the correct targeting of retinal ganglion cell (RGC) axons along the entire visual projection. We noted aberrant projections of RGC axons into the cerebral cortex, an area not normally targeted by RGC axons. The optic chiasm was expanded along the rostro-caudal axis (similar to Slit mutant mice, Plump, A.S., Erskine, L., Sabatier, C., Brose, K., Epstein, C.J., Goodman, C.S., Mason, C.A., Tessier-Lavigne, M., 2002. Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system. Neuron 33, 219-232), with ectopic crossing points, and some axons projecting caudally toward the corticospinal tract. Further, we found that axons exuberantly projected into the diencephalon. These defects were more pronounced in Robo2 than Robot knockout animals, implicating Robo2 as the predominant Robo receptor in visual system development. (c) 2007 Elsevier Inc. All rights reserved.