Regulation of the DLK-1 pathway in axon regeneration

描述（由申请人提供）：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，通过DLK-1途径调节cebp-1 mRNA稳定和局部蛋白翻译是轴突再生成功的必要条件。然而，轴突损伤如何激活DLK信号通路，DLK-1如何调控多个下游通路，以及CEBP-1的下游靶点是什么仍不清楚。在这项研究中，我提出了实验来解决这些问题。最终，我想找到一种调节DLK-1通路促进C轴索损伤后功能恢复的方法。秀丽线虫和老鼠。该奖项指导阶段的重点将是DLK-1的激活机制和揭示DLK-1负调控基因。在独立阶段，我将进一步研究DLK-1负调控基因的调控机制，系统分析CEBP-1的转录靶点和轴突功能。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: This project will address the regulatory mechanisms of the DLK-1 signaling pathway in axon regeneration. Because the DLK-1 signaling pathway is essential for axon regeneration, my studies will likely provide new clues for curing axonal injuries. This signaling pathway is also important for many other processes, such as synapse formation, axon growth and axon degeneration. Therefore my studies may also shed light on neuronal development and learning memory mechanisms.