The long-term goal of the research proposed in this application is the identification and description of genetic and epigenetic factors which result in tissue-specific gene expression in developing neurons of the mammalian nervous system.
The specific aims i nclude 1) the description, at the molecular level, of the gene encoding the neuron-specific protein Synapsin I; 2) definition of the molecular mechanisms that result in the developmentally regulated, tissue-specific expression of this gene. The tools of molecular genetics and recombinant DNA technology will be applied in order to achieve these goals. Restriction enzyme mapping Southern blotting and DNA sequencing will be used to describe the synapsin gene. The mechanisms regulating synapsin gene expression will be studied through 1) construction of deletion mutants in synapsin gene regulatory sequences and the analysis of their expression in transfected PC12 cells, 2) assessment of the affect of trophic factors (NGF) and substrate (laminin) on synapsin gene expression in vitro. Achieving these goals will contribute to our overall knowledge of the molecular mechanisms regulating the successful development and functioning of the nervous system and will therefore give insight into diseases which result from a defect in these mechanisms.
