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.
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