| The function of the nervous system depends upon the establishment and maintenance of functional connections between neurons, which are formed by axons. The outgrowth of these axons is driven by the polymerization and dynamics of cytoskeletal proteins. Neurofilaments (NFs) are major components of the axon cytoskeleton, and the expression of their subunits, neuronal intermediate filament (nIF) proteins, is highly regulated during axon development and regeneration. Despite this, the function of nIF proteins in growing axons is poorly understood. To enhance our understanding of the role of nIF proteins in axon growth, I examined the contribution of the nIF protein peripherin to axon growth in developing and regenerating axons of the frog, Xenopus laevis.; In Chapter 1, a review of the current literature provides the background necessary for the interpretation of my data. In Chapter 2, I describe the expression of peripherin during development and into adulthood by in situ hybridization and immunohisto-chemistry and compare it to that of other nIF proteins. Peripherin mRNA appears in neurons before the other nIF mRNAs do and before axons are formed, and it is especially abundant during axon outgrowth, suggesting that peripherin plays an important role in axon elongation. In addition, peripherin is present in proliferating neural precursors and glia, indicating that it may be involved in the formation of neural processes in general.; To investigate whether this increase in peripherin was also seen in regenerating CNS axons, I examined peripherin mRNA and protein expression in retinal ganglion cells (RGCs) after crushing the optic nerve. In Chapter 3, I show that peripherin expression increases dramatically and early in regenerating RGCs, supporting the idea that peripherin is important in axon elongation. In addition, I demonstrate that the mix of nIF mRNAs changes characteristically during regeneration. Collectively, these studies confirm a role for peripherin in early axon growth. Furthermore, they suggest that the intricate regulation of nIF expression serves to tailor NFs to specific functions during axon elongation and maturation. |
