Neurogenetics of Drosophila
In my laboratory we are applying the techniques of Drosophila genetics to problems in developmental neurobiology. This work stems from a project in which we isolated and characterized mutations that disrupt neural circuitry. The goal of this project is to identify genes involved in directing the precision of synaptic connectivity. It is hoped that this approach will help identify the molecules required for proper axon projection and the establishment of connections with the appropriate synaptic targets. The mutations we are working on were identified in a screen that assays the proper function of the tactile sensory-CNS motor circuitry required for the leg movements performed during grooming behavior. Mutations that disrupt behavior have also been assayed for their effect on the anatomy and physiology of identified neurons. One of the mutations we have identified, called midline-uncoordinated (muc), alters the axonal projections of an identified sensory neuron in adults. These animals also have interesting behavior: defects involving bilateral leg rubbing and abnormal reflexes to stimulation of individual sensory neurons. We are further describing the defects in neural `wiring' in muc and have initiated a molecular analysis of the gene. Many of the mutations we have isolated, including muc, were induced by single P element insertion mutagenesis. This technique provides mutations that are genetically valuable due to the ease of creating derivative alleles and because the insertion allows direct cloning of the flanking chromosomal sequences. Thus the project is designed to identify genes that function in the development of the nervous system in such a way that we can make full use of the powerful tools of Drosophila molecular genetics for their analysis.
Phillis, R.W., A.T. Bramlage, C. Wotus, A. Whittaker, L.S. Gramates, D. Seppala, F. Farahanchi, P. Caruccio and R.K. Murphey. 1993. Isolation of mutations affecting neural circuitry required for grooming behavior in Drosophila melanogaster. Genetics 133 (in press).
Robertson, H.M., C.R. Preston, R.W. Phillis, D. Johnson-Schlitz, W.K. Benz, and W.R. Engels. 1988. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics 118: 461-470.
Engels, W.R., W.K. Benz, C.R. Preston, P.L. Graham, R.W. Phillis and H.M. Robertson. 1987. Somatic effects of P element activity in Drosophila melanogaster. Genetics 117: 745-757.
Gorczyca, M.G., R.W. Phillis and V. Budnik. 1994. The role of tinman, a mesodermal cell fate gene, in axon pathfinding during the development of the transverse nerve in Drosophila. Development 120: 2143-2152.
Phillis, R., Statton, D., Caruccio, P., and R.K. Murphey. 1996. Mutations in the 8kDa dynein light chair gene disrupt sensory axon projections in the Drosophila imaginal CNS. Development 122: 2955-2963.