The role of Swiss cheese, the Drosophila homologue of Neuropathy target esterase, in glia development. Sudeshna Dutta, Janis McFerrin, Bruce Patton, Doris Kretzschmar. CROET, Oregon Health and Science University, Portland, OR.

   Neuropathy target estarase (NTE), a molecular target of organophosphates (OP) found in pesticides and nerve gases, is an important factor in an induced delayed neuropathy (OPIDN) and an inherited spastic paraplegia in humans. OPIDN is characterized by axonal degeneration mainly of motoneurons. Similarly, loss of the Drosophila homologue of NTE, Swiss Cheese (SWS) causes progressive neurodegeneration and also glial degeneration in flies and we have previously shown a cell autonomous requirement of SWS in both cell types in the adult brain of Drosophila. Using cell type specific down regulation of SWS, we can now specifically address its requirement in glia. Our recent findings demonstrate that only one type of glia, the ensheathing glia is affected by SWS down-regulation. We are also investigating what functional domains of SWS are required in glia, by using point mutations in the kinase domain and esterase domain of SWS in these glia specific knock-downs. Similar to flies, our findings in mice also demonstrate the presence of SWS/NTE in glia cells in the sciatic nerve, suggesting a conserved role of SWS in glia in higher vertebrates. NTE is expressed in high levels in nonmyelinating Schwann Cell (SC) and lower levels in myelinating SC. These studies, using both Drosophila and mouse models, will help us to understand the importance of the SWS protein in glia, its role in axonal-glial interaction and its pathogenic function in inherited spastic paraplegia and OPIDN in humans.