Krüppel样因子(KLFs)已成为各种细胞过程的重要转录调节因子,包括神经发育。其中一些已被描述为参与脊椎动物中枢神经系统(CNS)轴突再生的内在因素。斑马鱼以其在成年期再生几种组织的能力而闻名,包括中枢神经系统,在脊椎动物进化过程中丧失的能力,在成年哺乳动物中不存在。KLFs在这种差异能力中可以发挥的作用仍然未知。因此,在这项研究中,我们分析了在视网膜发育过程中和轴突损伤后参与轴突再生的某些KLFs(KLFs6,7,9和13)的内源性反应.结果表明,Klfs6、7和13的表达在小鼠发育中的视网膜中降低,而在斑马鱼中没有降低,而Klf9的mRNA水平在两个物种中都强烈增加。使用视神经挤压(ONC)作为损伤模型进一步分析了对损伤的反应。我们在急性期(小时)的分析显示,仅在斑马鱼视网膜中诱导Klfs6和7表达,而Klfs9和13mRNA水平在两个物种中都增加。对慢性反应(天)的进一步分析表明,斑马鱼和小鼠视网膜中Klf6的mRNA水平短暂增加,而视神经损伤后Klf7的下降较晚。此外,分析显示Klf9的表达减少,而斑马鱼视网膜中的Klf13对视神经损伤的反应增加,但在小鼠中保持不变。总之,这些发现支持KLFs可能在鱼和小鼠表现出的不同轴突再生能力中发挥作用的假设。
The Krüppel-like factors (KLFs) have emerged as important transcriptional regulators of various cellular processes, including neural development. Some of them have been described as intrinsic factors involved in axon regeneration in the central nervous system (CNS) of vertebrates.
Zebrafish are known for their ability to regenerate several tissues in adulthood, including the CNS, a capability lost during vertebrate evolution and absent in adult mammals. The role that KLFs could play in this differential ability remains unknown. Therefore, in this study, we analyzed the endogenous response of certain KLFs implicated in axon regeneration (KLFs 6, 7, 9, and 13) during retina development and after axon injury. The results showed that the expression of Klfs 6, 7, and 13 decreases in the developing retina of mice but not in
zebrafish, while the mRNA levels of Klf9 strongly increase in both species. The response to injury was further analyzed using optic nerve crush (ONC) as a model of lesion. Our analysis during the acute phase (hours) demonstrated an induction of Klfs 6 and 7 expression exclusively in the
zebrafish retina, while Klfs 9 and 13 mRNA levels increased in both species. Further analysis of the chronic response (days) showed that mRNA levels of Klf6 transiently increase in the retinas of both
zebrafish and mice, whereas those of Klf7 decrease later after optic nerve injury. In addition, the analysis revealed that the expression of Klf9 decreases, while that of Klf13 increases in the retinas of
zebrafish in response to optic nerve injury but remains unaltered in mice. Altogether, these findings support the hypothesis that KLFs may play a role in the differential axon regeneration abilities exhibited by fish and mice.