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Category: Blu-ray.The molecular mechanisms by which intracellular signaling pathways mediate axon outgrowth following injury remain an open question. The PI has recently found that expression of an activated form of the GSK3β kinase in injured dorsal root ganglion (DRG) neurons promotes axon growth that is dependent upon the expression of specific signaling molecules. The experiments proposed in this application will test the hypothesis that GSK3 regulates axon outgrowth in the injured DRG neuron by selectively phosphorylating and activating the transcription factor SRF. The specific aims of this proposal are to (1) determine the mechanism by which GSK3 regulates SRF function and mRNA expression during axon outgrowth after injury; and (2) to determine the role of GSK3/SRF signaling in the promotion of axon outgrowth and sprouting by injury. The focus of this work will be to define the role of GSK3/SRF signaling in axon growth and its relationship to the pro-growth factor Ang-1/Tie2 signaling pathway. The proposal incorporates microarray analysis of gene expression to identify potential downstream effector molecules that mediate the effects of GSK3/SRF signaling on axon outgrowth and sprouting. The overall goal of this project is to gain a greater understanding of how GSK3 regulates axon outgrowth. The experiments proposed in this application will be a major first step in defining the mechanism by which GSK3 can promote axon growth and sprouting in the injured DRG neuron.Q:
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