The long term goal of the proposal is to understand how the specific patterns of synaptic connectivity between neurons are established. The orderliness of this process is crucial as mistakes in connectivity can disrupt neural circuits, and block proper function of the nervous system in all organisms including man. How neurons select their synaptic partners at a molecular level remains largely unsolved. The applicant and his colleagues will apply molecular, genetic, and electrophysiological methods to directly assay genes that function in the process of establishing synaptic connections. In this project, they will focus on the sensory nervous system of adult Drosophila. They have characterized a set of enhancer trap insertion lines that are expressed in specific subsets of sensory axons. Mutations caused by the insertion or excision of the P element will be characterized to determine the nature of the defects they cause in neuronal differentiation. Characterization of the genes identified by these insertions may aid in the understanding of the molecular processes that establish specific patterns of synaptic connections. Cloning and sequencing of the relevant genes will provide a description of their products. Finally, anatomical and electrophysiological assays for the function of the genes will be developed. Since many of the genes will be common to humans and flies, the identification of these genes may prove to be of clinical relevance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015571-20
Application #
2839277
Study Section
Neurology C Study Section (NEUC)
Program Officer
Michel, Mary E
Project Start
1979-07-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
2000-11-30
Support Year
20
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
01003
Allen, Marcus J; Murphey, R K (2007) The chemical component of the mixed GF-TTMn synapse in Drosophila melanogaster uses acetylcholine as its neurotransmitter. Eur J Neurosci 26:439-45
Allen, M J; Shan, X; Murphey, R K (2000) A role for Drosophila Drac1 in neurite outgrowth and synaptogenesis in the giant fiber system. Mol Cell Neurosci 16:754-65
Murphey, R K; Caruccio, P C; Getzinger, M et al. (1999) Dynein-dynactin function and sensory axon growth during Drosophila metamorphosis: A role for retrograde motors. Dev Biol 209:86-97
Allen, M J; Shan, X; Caruccio, P et al. (1999) Targeted expression of truncated glued disrupts giant fiber synapse formation in Drosophila. J Neurosci 19:9374-84
Trimarchi, J R; Jin, P; Murphey, R K (1999) Controlling the motor neuron. Int Rev Neurobiol 43:241-64
Trimarchi, J R; Murphey, R K (1997) The shaking-B2 mutation disrupts electrical synapses in a flight circuit in adult Drosophila. J Neurosci 17:4700-10
Reddy, S; Jin, P; Trimarchi, J et al. (1997) Mutant molecular motors disrupt neural circuits in Drosophila. J Neurobiol 33:711-23
Phillis, R; Statton, D; Caruccio, P et al. (1996) Mutations in the 8 kDa dynein light chain gene disrupt sensory axon projections in the Drosophila imaginal CNS. Development 122:2955-63
Phillis, R W; Bramlage, A T; Wotus, C et al. (1993) Isolation of mutations affecting neural circuitry required for grooming behavior in Drosophila melanogaster. Genetics 133:581-92
Merritt, D J; Murphey, R K (1992) Projections of leg proprioceptors within the CNS of the fly Phormia in relation to the generalized insect ganglion. J Comp Neurol 322:16-34

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