Regulation of the DLK-1 pathway in axon regeneration

项目总结 轴突损伤，如脊髓损伤，是常见的健康问题。为了找到治疗轴突损伤的方法，我们 需要了解轴突再生的机制。我之前的研究表明，CEBP-1的调节 成功的轴突需要DLK-1途径的mRNA稳定和局部蛋白质翻译 再生。然而，轴突损伤如何激活DLK信号通路，DLK-1如何调节 下游途径，以及CEBP-1的下游目标是什么，目前仍不清楚。在这项研究中，我建议 解决这些问题的实验。最终，我想找到一种方法来调节DLK-1通路以 促进线虫和小鼠轴突损伤后的功能恢复。《被辅导者》中的重点 该奖项的阶段将是关于DLK-1的激活机制和发现DLK-1的负调控 基因。在独立阶段，我将进一步研究DLK-1负调控的调控机制 基因，并系统分析CEBP-1的转录靶点和轴突功能。

PROJECT SUMMARY Axonal injuries, such as spinal cord injury, are common health issues. To find a way to cure axonal injuries we need to know the mechanisms of axon regeneration. My previous studies showed that regulation of cebp-1 mRNA stabilization and local protein translation by the DLK-1 pathway is required for successfully axon regeneration. However, how axonal injury activates the DLK signaling pathway, how DLK-1 regulates multiple downstream pathways, and what are CEBP-1 downstream targets are still unclear. In this study, I propose experiments to address these questions. Ultimately, I want to find a way to modulate the DLK-1 pathway to promote functional recovery after axonal injury in C .elegans and the mouse. The emphasis in the mentored phase of the award will be on the activation mechanisms of DLK-1 and uncovering DLK-1 negatively regulated genes. In the independent phase, I will further study the regulatory mechanisms of DLK-1 negatively regulated genes, and systematically analyze CEBP-1 transcriptional targets and axonal functions.