Neuronal development and regeneration is accompanied by marked changes in the expression and organization of cytoskeletal proteins. The contribution of microtubule associated proteins (MAPs) to this process is significant since these proteins are major structural components of neurons and play important roles in defining neuronal morphology, axonal transport and axonal growth. These proteins, specifically MAP1B, tau, and MAP1A, modify the assembly and organization of microtubules and thus modulate the balance between stability and plasticity of the axonal cytoskeleton. Our general working hypothesis is that a successful regenerative strategy requires a specific program of changes in gene expression, post-translational modifications, and axonal transport that initially serves to facilitate elongation by promoting dynamic remodeling, and at later stages inducing stability and maturation. The in vivo experiments include studies on regulation, axonal transport, protein phosphorylation, and the function of the three axonal MAPs in the rat dorsal root ganglia (DRG) following injury. Regeneration will be initiated by peripheral or central nerve lesions, and sprouting by removal of adjacent ganglia. The in vitro experiments include studies on the role of MAPs during regeneration of cultured adult DRG neurons using antisense oligonucleotides and the microinjection of antibodies and peptides. These studies will improve our understanding of the role of cytoskeletal gene expression in regeneration and will provide insight into promoting successful regeneration in the central nervous system.
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