The experiments proposed herein are designed to further our understanding of development and function of monoamine neurons and monoamines in the nervous system. Aberrant neurotransmitter levels and defects in monoamine neurons have been observed in association with a number of human pathologies (e.g. Parkinson's disease, phenylketoneurea, schizophrenia etc.). The long term objectives of the proposed research are to develop genetic variants and molecular probes that will allow manipulation of the biogenic amine synthesis in the model system, Drosophila melanogaster, for each amine (serotonin, dopamine and octopamine), and to perturb the transmitter phenotype of monoamine containing neurons by creation of novel genetic variants. Biological consequences of perturbations in amine level and amine specificity for each individual neuronal subsets will be analyzed in the conventional and novel genetic variants. Specifically molecular genetics of genes encoding tryptophan hydroxylase, tyrosine hydroxylase and tyramine beta hydroxylase will be developed, so that it will be possible to manipulate synthesis of each amine, and promoter sequences that can confer cell type specific expression are cloned and characterized. These goals will be approached using experimental strategies that depend on molecular and genetic methodologies, many of which are unique to Drosophila. These methodologies will be used in conjunction with the current anatomical, histochemical, biochemical and immunohistochemical approaches. Molecular probes and genetic variants developed here will augment and complement the current cellular and biochemical understanding of by far the best characterized set of neurons in the nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023510-06
Application #
3407077
Study Section
Neurology C Study Section (NEUC)
Project Start
1986-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Monastirioti, M; Linn Jr, C E; White, K (1996) Characterization of Drosophila tyramine beta-hydroxylase gene and isolation of mutant flies lacking octopamine. J Neurosci 16:3900-11
Monastirioti, M; Gorczyca, M; Rapus, J et al. (1995) Octopamine immunoreactivity in the fruit fly Drosophila melanogaster. J Comp Neurol 356:275-87
Neckameyer, W S; White, K (1993) Drosophila tyrosine hydroxylase is encoded by the pale locus. J Neurogenet 8:189-99
Neckameyer, W S; White, K (1992) A single locus encodes both phenylalanine hydroxylase and tryptophan hydroxylase activities in Drosophila. J Biol Chem 267:4199-206
Gorczyca, M G; Budnik, V; White, K et al. (1991) Dual muscarinic and nicotinic action on a motor program in Drosophila. J Neurobiol 22:391-404
Valles, A M; White, K (1990) Serotonin synthesis and distribution in Drosophila dopa decarboxylase genetic mosaics. J Neurosci 10:3646-52
Budnik, V; Wu, C F; White, K (1989) Altered branching of serotonin-containing neurons in Drosophila mutants unable to synthesize serotonin and dopamine. J Neurosci 9:2866-77
Budnik, V; White, K (1988) Catecholamine-containing neurons in Drosophila melanogaster: distribution and development. J Comp Neurol 268:400-13
Valles, A M; White, K (1988) Serotonin-containing neurons in Drosophila melanogaster: development and distribution. J Comp Neurol 268:414-28
Budnik, V; White, K (1987) Genetic dissection of dopamine and serotonin synthesis in the nervous system of Drosophila melanogaster. J Neurogenet 4:309-14

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