Haverford College Department of Biology, Haverford, Pennsylvania 19041, USA.
Dev Dyn. 2010 Nov;239(11):2921-32. doi: 10.1002/dvdy.22430.
The role of classic morphogens such as Sonic hedgehog (Shh) as axon guidance cues has been reported in a variety of vertebrate organisms (Charron and Tessier-Lavigne [2005] Development 132:2251-2262). In this work, we provide the first evidence that Xenopus sonic hedgehog (Xshh) signaling is involved in guiding retinal ganglion cell (RGC) axons along the optic tract. Xshh is expressed in the brain during retinal axon extension, adjacent to these axons in the ventral diencephalon. Retinal axons themselves express Patched 1 and Smoothened co-receptors during RGC axon growth. Blocking Shh signaling causes abnormal ventral pathfinding, and targeting errors at the optic tectum. Misexpression of exogenous N-Shh peptide in vivo also causes pathfinding errors. Retinal axons grown in culture respond to N-Shh in a dose-dependent manner, either by decreasing extension at lower concentrations, or retracting axons in the presence of higher doses. These data suggest that Shh signaling is required for normal RGC axon pathfinding and tectal targeting in the developing visual system of Xenopus. We propose that Shh serves as a ventral optic tract repellent that helps to define the caudal boundary for retinal axons in the diencephalon, and that this signaling is also required for initial target recognition at the optic tectum.
经典形态发生素(如 Sonic hedgehog,Shh)作为轴突导向线索的作用已在多种脊椎动物中得到报道(Charron 和 Tessier-Lavigne [2005] Development 132:2251-2262)。在这项工作中,我们提供了第一个证据,表明 Xenopus sonic hedgehog(Xshh)信号参与引导视网膜神经节细胞(RGC)轴突沿着视路生长。在视网膜轴突延伸期间,Xshh 在脑中表达,与腹侧间脑的这些轴突相邻。视网膜轴突本身在 RGC 轴突生长过程中表达 Patched 1 和 Smoothened 共受体。阻断 Shh 信号会导致视轴突异常的腹侧寻路和视顶盖的靶向错误。体内异位表达外源 N-Shh 肽也会导致寻路错误。体外培养的视网膜轴突对 N-Shh 表现出剂量依赖性反应,较低浓度下会减少延伸,而较高浓度下则会缩回轴突。这些数据表明,Shh 信号对于 Xenopus 发育中视觉系统的正常 RGC 轴突寻路和视顶盖靶向是必需的。我们提出 Shh 作为一种腹侧视路排斥物,有助于在间脑中为视网膜轴突定义尾部边界,并且这种信号对于视顶盖的初始靶标识别也是必需的。