Regulation of the DLK-1 pathway in axon regeneration

DLK-1 通路在轴突再生中的调节

• 批准号: 8802904
• 负责人: Dong Yan
• 金额: $ 24.9万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8802904
• 关键词: Address; Affect; Award; Axon; Calcium; Cell Nucleus; ChIP-on-chip; Dimerization; Event; Gene Expression; Genes; Genetic Screening; Genomics; Health; Human; Injury; Knowledge; Lasers; Learning; Leucine Zippers; Light; Mediating; Memory; Mentors; Messenger RNA; Methods; Microsurgery; Molecular; Molecular Genetics; Mus; Nuclear; Output; Pathway interactions; Phase; Phenotype; Phosphotransferases; Postdoctoral Fellow; Process; Proteins; Recovery of Function; Regulation; Regulatory Pathway; Research; Signal Pathway; Signal Transduction; Single Nucleotide Polymorphism Map; Spinal cord injury; Synapses; Technology; Translations; Work; axon growth; axon regeneration; axonal degeneration; in vivo imaging; interest; loss of function; mutant; neuron development; research study; synaptogenesis; transcription factor

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.

项目摘要 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， 需要了解轴突再生的机制我以前的研究表明调节cebp-1 通过DLK-1途径的mRNA稳定和局部蛋白翻译是成功轴突生长所必需的。 再生然而，轴突损伤如何激活DLK信号通路，DLK-1如何调节多种 CEBP-1的下游通路以及CEBP-1的下游靶点仍不清楚。在这项研究中，我建议 实验来解决这些问题。最终，我想找到一种方法来调节DLK-1通路， 促进线虫和小鼠轴突损伤后的功能恢复。受指导者的重点 该奖项的阶段将是对DLK-1的激活机制和揭示DLK-1负调控 基因.在独立研究阶段，我将进一步研究DLK-1负调控的调控机制 基因，并系统地分析CEBP-1的转录靶点和轴突功能。