The long-term objective of the work proposed here is to understand the role of intermediate filaments (IF) in neural development. IF are thought to be structurally important in the development and maintenance of cell morphology. Studies have shown that the expression of proteins that compose IF changes as cells differentiate. This data indicates that IF may be involved in functions specific to the differentiated state of cells or to the process of differentiation. The goals pertinent to the work described in this application are to study the importance of one particular IF protein the 57kD neural IF protein (NIFP) to differentiation in vivo and in vitro. The distribution of the 57kD NIFP will be examined during development of the rat in the embryonic and early postnatal period. The relationship of this protein to the ontogeny and differentiation of neurons will be examined in tissue sections using antibodies to the 57kD NIFP as probes. To determine the role of the 57kD NIFP in processes involved in differentiation, the effects of a disrupted IF network on nerve growth factor-induced differentiation in the neuron-like cell line PC12 will be determined. IF disruption will be accomplished via gene transfer of deletion mutants of the 57kD NIFP cDNA. The study of this neural IF protein is expected to yield information on neural development and the cellular components involved. These findings will have obvious relevance to the development of the normal embryo but also should add to our knowledge of the neuronal intermediate filaments. Analyses of the role of these structures in normal neuronal function should lead to an improved understanding of the processes leading to abnormal accumulations of IF. These accumulations are prominent pathologic findings in many important degenerative neurologic diseases.
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