One of the major unsolved problems in biology is the cause for a variety of human neurological defects. Some of these defects must be due to mutations that cause miswiring of the nervous system and the long range goal of this project is to discover such mutations. Many of the molecules important to the assembly of the nervous system are thought to be common throughout the animal kingdom. This project will take advantage of the well known genetics of the fruitfly Drosophila melanogaster to search for the genes, and the molecules they encode that are important to the assembly of the nervous system. P elements are used as mutagens and then mutant animals are screened for neurological defects. Once a mutant is in hand, single neurons will be stained intracellularly to characterize the anatomy of the synaptic circuitry. Intracellular recording methods are adapted to flies in order to characterize the function of the sensory synapses in these reflex circuits. These methods are then used to compare mutants to wild type specimens and thereby demonstrate the nature of the genetic lesions. The modified P element used as a mutagen carries a lacZ reporter gene which can reveal expression patterns of genes at the insertion site. The P element also carries sequences which allow rapid cloning of DNA flanking the insertion site. Through cloning and the subsequent molecular analysis of the genes we identify, we will determine the nature of their protein products and characterize their patterns of expression in order to understand the nature of their function in properly """"""""wiring"""""""" the nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015571-15
Application #
3396329
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1979-07-01
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
15
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
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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