The goal of this program is an increased understanding of the principles underlying the development of nervous systems. Investigations are planned for: a) the generation and migration of neurons; b) neuronal gene expression and differentiation, and c) synaptogenesis and the maintenance of synaptic junctions. These studies will be conducted by a multidisciplinary research group using contemporary techniques. In Project 1, 3H-thymidine radioautography will be used in conjunction with immunocytochemistry to compare the generation and differentiation of neurons that exhibit two different neurotransmitter phenotypes; namely acetylcholine (ACh) or gamma-aminobutyric acid (GABA). These studies will be conducted in brain regions that allow developmentally interesting comparisons, as well as in regions where ACh and GABA neurons have been implicated in neurological disorders such as Alzheimer's disease and epilepsy.
The aims of Project 2 are to investigate the development expression of nerve growth factor (NGF), and to define the role(s) of NGF in Drosophila neurodevelopment in vitro. Project 3 seeks an increased understanding of gene expressions underlying the early development of the neuronal phenotype. Studies of the biochemical nature and developmental regulation of neuron specific gene expression will be conducted in vitro on cells derived from Drosophila embryos. An investigation of the developmental expression of the cholinergic neuronal phenotype is proposed in Project 4. Monoclonal antibodies will be used to study the developmental expression of choline acetyltransferase (ChAT) in conjunction with other antigens of this phenotype.
The aims of Project 5 are to characterize developmental changes in fast axonal transport of membrane and secretory proteins in frog spinal cord, and to examine thyroid hormonal control of the synthesis, post-translational modification and transport of proteins during neurodevelopment. Multidisciplinary investigations of the formation and maintenance of synaptic junctions in Drosophila embryo cell cultures are proposed in Project 6. These studies will analyze a variety of aspects of synaptogenesis, including the de novo formation of synaptic vesicles, as well as the packaging, transport and release of transmitter. Although the focus of this program is normal development, it is anticipated that it will contribute basic information that is relevant to understanding certain neurological disorders.
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