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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025050-04
Application #
3410140
Study Section
Neurology C Study Section (NEUC)
Project Start
1987-09-10
Project End
1991-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Melloni Jr, R H; Apostolides, P J; Hamos, J E et al. (1994) Dynamics of synapsin I gene expression during the establishment and restoration of functional synapses in the rat hippocampus. Neuroscience 58:683-703
Melloni Jr, R H; DeGennaro, L J (1994) Temporal onset of synapsin I gene expression coincides with neuronal differentiation during the development of the nervous system. J Comp Neurol 342:449-62
Melloni Jr, R H; Hemmendinger, L M; Hamos, J E et al. (1993) Synapsin I gene expression in the adult rat brain with comparative analysis of mRNA and protein in the hippocampus. J Comp Neurol 327:507-20
Melloni Jr, R H; Estes, P S; Howland, D S et al. (1992) A method for the direct measurement of mRNA in discrete regions of mammalian brain. Anal Biochem 200:95-9
Howland, D S; Hemmendinger, L M; Carroll, P D et al. (1991) Positive- and negative-acting promoter sequences regulate cell type-specific expression of the rat synapsin I gene. Brain Res Mol Brain Res 11:345-53
Kirchgessner, C U; Trofatter, J A; Mahtani, M M et al. (1991) A highly polymorphic dinucleotide repeat on the proximal short arm of the human X chromosome: linkage mapping of the synapsin I/A-raf-1 genes. Am J Hum Genet 49:184-91