The operation of the nervous system depends on nerve cells communicating with each other through a fine network of cellular extensions known as axons and dendrites. Axons are usually longer extensions and their initial growth constitutes one of the crucial steps in determining the organization of the nervous system. A growth associated protein, known as GAP-43, enriches axons of nerve cells and is associated with axonal growth. While the relationship of this protein to growth and the biochemistry of this protein have been well established, little is known about the mechanisms that regulate the levels of GAP-43 in nerve cells. Previous work has indicated that the amounts of this protein are determined by the levels of messenger RNA, the intermediary molecule that links the activity of the gene with the synthesis of the protein. The investigator plans to study how the expression of GAP-43 is regulated by focusing on messenger RNA regulation. The levels of mRNA can be regulated at the level of synthesis or at the level of degradation. Preliminary work from the investigator's laboratory indicates that the key control point in the expression of GAP-43 may not depend on the level of synthesis but on the regulation of the stability of messenger RNA. The study will determine to what extent synthesis and degradation mechanisms participate in the control of GAP-43 mRNA levels during neuronal differentiation, in vivo and in cultures of isolated cells. These studies will provide fundamental information on the mechanisms that govern GAP-43 levels which will set the basis for future studies on the specific molecular aspects of these regulatory events. The elucidation of the mechanisms that regulate the expression of GAP-43 and other growth-related proteins will not only bring new insights into the question of gene expression control during neuronal differentiation, but will contribute to the understanding of the molecular events that underlie the development of the nervous system.
