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.
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.
|Meng, Lingfeng; Mulcahy, Ben; Cook, Steven J et al. (2015) The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons. Cell Rep 11:1737-48|
|Yan, Dong; Jin, Yishi (2012) Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform. Neuron 76:534-48|