Slits contribute to the guidance of retinal ganglion cell axons in the mammalian optic tract

Slits contribute to the guidance of retinal ganglion cell axons in the mammalian optic tract
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DOI:
10.1016/j.ydbio.2006.06.017
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发表时间:
2006-08-15
影响因子:
2.7
通讯作者:
Erskine, Lynda
Erskine, Lynda
中科院分区:
生物学3区
文献类型:
--
作者:
Thompson, Hannah;Barker, David;Erskine, Lynda

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RGC轴突在视束中以与抑制RGC轴突生长的可溶性因子在下丘脑和上丘脑中的表达相关的方式延伸。此外,虽然RGC轴突延伸到端脑附近,但它们通常不会生长到该组织中。在这里,我们表明,slit 1和slit 2,已知的化学排斥RGC轴突在间脑和端脑的特定区域表达,帮助调节视束的发展。在缺乏slit 1和slit 2的小鼠中,RGC轴突的一个子集延伸到端脑中,并沿着软膜表面生长,但不会更深地进入该组织。令人惊讶的是,在slit 1-/-、slit 2 +/-和slit 1/2 -/-胚胎的端脑中发生了明显的引导错误,这表明Slits的精确水平对于确定单个轴突遵循的路径至关重要。在缺乏slit 1和slit 2的小鼠中,RGC轴突的一个子集也异常地投射到上丘脑、松果体和背中线。然而,许多轴突到达它们的主要目标,上级丘。这表明,裂隙在指导视束内的交叉后RGC轴突的引导中起重要作用,但不是靶神经支配所需的。(c)2006年爱思唯尔公司All rights reserved.
RGC axons extend in the optic tracts in a manner that correlates with the expression in the hypothalamus and epithalamus of a soluble factor inhibitory to RGC axon outgrowth. Additionally, although the RGC axons extend adjacent to the telencephalon, they do not normally grow into this tissue. Here, we show that slit1 and slit2, known chemorepellents for RGC axons expressed in specific regions of the diencephalon and telencephalon, help regulate optic tract development. In mice lacking slit1 and slit2, a subset of RGC axons extend into the telencephalon and grow along the pial surface but not more deeply into this tissue. Surprisingly, distinct guidance errors occur in the telencephalon of slit1-/-; slit2 +/- and slit1/2 -/- embryos, suggesting that the precise level of Slits is critical for determining the path followed by individual axons. In mice lacking both slit1 and slit2, a subset of RGC axons also project aberrantly into the epithalamus, pineal and across the dorsal midline. However, many axons reach their primary target, the superior colliculus. This demonstrates that Slits play an important role in directing the guidance of post-crossing RGC axons within the optic tracts but are not required for target innervation. (c) 2006 Elsevier Inc. All rights reserved.