Many genes that participate in embryonic development also influence human health. Scientists utilise specific tools to study development in model organisms. Mutagenesis screens in particular offer an unbiased means of dissecting the genetic components of development, for no prior knowledge of the participating genes is required. Alternative approaches such as reverse genetics and controlled misexpression of heterologous genes can serve to complement the analysis of mutant phenotypes in model organisms. The zebrafish has emerged as a powerful system for studies of vertebrate biology and organogenesis. External development and optical clarity allow the easy and visual analysis of early developmental processes. Short generation time, the possibility to achieve large scale mutagenesis screens and generation of thousands of individuals in a relatively inexpensive way are characteristics that make this and ideal model system. Although the zebrafish is poised to contribute greatly to our understanding of organ development, alternative well developed technologies for reverse genetic analysis are lacking. Gene redundancy due to a partially duplicated genome presents a severe hurdle that must be overcome. When the sequence of a gene is known, however, controlled misexpression using the GAL4/UAS system can link the gene's structure to its function, and this methodology is being used with the great success in Drosophila. The GAL4/UAS system is not well advanced in the zebrafish, but shows promise. Also, selective misexpression of genes allows organs to be dissected as genetic modules, leaving the remainder of the animal to develop normally. I propose to explore the process of organogenesis in the inner ear using the zebrafish (Danio rerio) as model system. This objective is dictated both by an intellectual desire to explain the ear's complexity and by an appreciation of the impact of genetic disease on human hearing: about one child in a thousand is born deaf or becomes deaf as a result of mutations in any of over 100 genes. The research group of Dr. A. J. Hudspeth, which has made seminal contributions to our understanding of the mechanism of hearing, has focussed during the past five years on deciphering the ear's development. To study the development and regeneration of the inner ear, I wish to further develop the GAL4/UAS technology and to use it to complement the current chemical-mutagenesis screen being conducted in the Hudspeth lab. This project will allow me to understand the genetics of a vertebrate system, and the development of a functional organ. Once fully developed, this methodology will enable conditional genetic alterations to study other organ systems and developmental processes.