Ohta K, Tannahill D, Yoshida K, Johnson A R, Cook G M, Keynes R J
Department of Anatomy, University of Cambridge, Downing Street, Cambridge, CB2 3DY, United Kingdom.
Dev Biol. 1999 Jul 1;211(1):124-32. doi: 10.1006/dbio.1999.9312.
During development of the vertebrate visual system, retinal ganglion cell (RGC) axons follow a precise path toward their midbrain targets. Although much is known about the cues that direct RGC axons once they have left the optic disc, less is known about the guidance of axons at earlier stages, when RGCs first send out their axons to navigate within the developing retina. Using collagen gel coculture experiments, we find that the embryonic lens produces a powerful diffusible repulsive activity for RGC axons. We also find that this activity is localized to the lens epithelium and not the lens fiber layer, while the pigmented epithelium and vitreous humour are devoid of activity. The further observation that the lens also chemorepels primary sensory axons, but does not repel olfactory bulb axons, shows that this activity is specific for subsets of axons. Our experiments have excluded two candidate repellents for RGC axons (collapsin-1/sema III and chondroitin sulfate proteoglycans). These results implicate the lens in the earliest stages of RGC axon guidance. One function of the lens repellent may be to prevent aberrant targeting toward the lens, and it may also be involved in the directional guidance of RGC axons toward the optic disc.
在脊椎动物视觉系统发育过程中，视网膜神经节细胞（RGC）轴突沿着精确路径朝向中脑靶标生长。尽管对于RGC轴突离开视盘后引导其生长的线索已有很多了解，但对于轴突在早期阶段（即RGC首次发出轴突并在发育中的视网膜内导航时）的导向了解较少。通过胶原凝胶共培养实验，我们发现胚胎晶状体对RGC轴突产生强大的可扩散排斥活性。我们还发现这种活性定位于晶状体上皮而非晶状体纤维层，而色素上皮和玻璃体则没有这种活性。进一步观察发现，晶状体对初级感觉轴突也有化学排斥作用，但不排斥嗅球轴突，这表明这种活性对轴突亚群具有特异性。我们的实验排除了RGC轴突的两种候选排斥因子（萎缩素-1/信号素III和硫酸软骨素蛋白聚糖）。这些结果表明晶状体在RGC轴突导向的最早阶段发挥作用。晶状体排斥因子的一个功能可能是防止轴突异常靶向晶状体，它也可能参与RGC轴突向视盘的定向引导。
