Regulation of axon growth and regeneration by the DLK signaling pathway

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Cells in multicellular organisms communicate with each other through a number of signaling molecules in order to control their growth, differentiation and metabolism. Information carried by these molecules is received at the cell surface and transmitted intracellularly by networks of signaling pathways that ultimately modulate gene expression. Alterations in the function of these pathways can lead to a spectrum of defects ranging from developmental abnormalities to numerous diseases, including cancer, diabetes and neurodegenerative disorders. With support from NSERC, we investigate the role and specific properties of a protein kinase named dual leucine zipper kinase (DLK), the upstream component of a signaling pathway involved in multiple biological functions. Interestingly, recent genetic studies carried out in different model organisms have highlighted a role for DLK in axon growth, a process crucial for development and repair of the nervous system. However, exactly how DLK mediates axon formation is an important question still not fully answered. Through transcriptome analysis of cultured neurons, our laboratory has recently demonstrated that DLK controls the expression of a number of genes associated with neuron projection and differentiation. Because such results provide an indication of the mechanism by which DLK contributes to axon growth, we propose to pursue our investigation by examining how these genes are regulated by DLK and how they might mediate the effects of DLK in neurons. It is anticipated that these studies will greatly expand our understanding of DLK’s action on axon growth and generate information of great value for regenerative medicine and neural tissue engineering.