Drosophotoxicology: the growing potential for Drosophila in neurotoxicology

Understanding neurotoxic mechanisms is a challenge of deciphering which genes and gene products in the developing or mature nervous system are targeted for disruption by chemicals we encounter in our environment. Our understanding of nervous system development and physiology is highly advanced due in large part to studies conducted in simple non-mammalian models. The paucity of toxicological data for the more than 80,000 chemicals in commercial use today, and the approximately 2000 new chemicals introduced each year, makes development of sensitive and rapid assays to screen for neurotoxicity paramount. In this article I advocate the use of Drosophila in the modern regimen of toxicological testing, emphasizing its unique attributes for assaying neurodevelopment and behavior. Features of the Drosophila model are reviewed and a generalized overall scheme for its use in toxicology is presented. Examples of where the fly has proven fruitful in evaluating common toxicants in our environment are also highlighted. Attention is drawn to three areas where development and application of the fly model might benefit toxicology the most: 1) optimizing sensitive endpoints for pathway-specific screening, 2) accommodating high throughput demands for analysis of chemical toxicant libraries, 3) optimizing genetic and molecular protocols for more rapid identification toxicant-by-gene interactions. While there are shortcomings in the Drosophila model, which exclude it from effective toxicological testing in certain arenas, conservation of fundamental cellular and developmental mechanisms between flies and man is extensive enough to warrant a central role for the Drosophila model in toxicological testing of today.