A role of Yamanaka's factor during fish optic nerve regeneration after nerve injury

与哺乳动物不同，鱼类的视神经在神经损伤后可以再生。我们对鱼类视神经的这种再生能力有一个假设，即鱼类中成熟的视网膜神经节细胞(RGCs)在视神经损伤后被重新编程为神经干细胞样细胞。为了证实这一假设，我们研究了视神经损伤后斑马鱼视网膜中Sox2、KLF4、c-myc和Nestin的表达水平。视神经切断后3d，视网膜组织中SOX2、KLF4和c-myc基因表达水平升高。视神经切断后4-5天，视网膜中神经干细胞标记物Nestin水平升高。这些分子均定位于视网膜节细胞。此外，我们还发现白血病抑制因子(LIF)是KLF4和Sox2的上游信号。在视网膜外植体的培养液中加入LIF，与不加LIF处理的对照组相比，可以看到明显的轴突生长。相反，抑制LIF信号导致抑制来自视网膜的轴突生长。因此，我们认为鱼的视神经再生能力是由于视神经损伤后成熟视网膜节细胞的再编程机制所致。

Unlike mammals, fish optic nerve can regenerate after nerve injury. We have a hypothesis of this regenerative capacity of fish optic nerve that mature retinal ganglion cells (RGCs) in fish are reprogrammed to neural stem-cell like cells by optic nerve injury. To certain this hypothesis, we investigated expression levels of sox2, klf4, c-myc and nestin in the zebrafish retina after optic nerve injury. The levels of sox2, klf4 and c-myc mRNA increased in the retina 3 days after axotomy. The level of a neural stem cell marker, nestin increased in the retina 4-5 days after axotomy. These molecules were all localized to the RGCs. Furthermore, we found that leukemia inhibitory factor (LIF) was positional as an upstream signal to the klf4 and sox2. In the presence of LIF in culture medium of retinal explant, a significant neurite outgrowth could be seen as compared to the no treatment, control. In contrast, the inhibition of LIF signals leaded to the suppression of neurite outgrowth from retina. Therefore, we conclude that the capability of fish optic nerve regeneration is due to reprograming mechanism of matured RGCs after optic nerve injury.