SEARCHING FOR VISUAL SYSTEM MUTATIONS IN ZEBRAFISH
JOHN E. DOWLING
Thirty years ago, Seymour Benzer showed that with simple behavioral tests it was possible to detect specific eye and brain mutations in the fruitfly, Drosophila melanogaster. A number of these behavioral mutants have proven to be exceptionally useful for unraveling signal transduction mechanisms in Drosophila as well as mechanisms underlying neuronal development. We have not had a vertebrate with which to carry out similar mutagenesis experiments, but zebrafish (Danio rerio) may be such an animal. Zebrafish are small (~1"), freshwater teleosts that can be grown inexpensively in large numbers. They have been successfully inbred, and have a relatively fast generation time (~3 months). They develop rapidly in eggs that are large (~1 mm in diameter) and transparent. Female zebrafish can lay as many as 100-200 eggs at weekly intervals, and efficient chemical mutagenesis techniques employing ethylnitrosurea have recently been developed.
Zebrafish are highly visual animals, exhibiting light responses after just 3 days of development, making them ideal for the genetic analysis of visual behavior. They have large eyes and are tetrachromatic, possessing ultraviolet-sensitive cones as well as red-, green-, and blue-sensitive cones. They also have abundant rods, and like other fish, their retinas continue to grow for the life of the animal. Our group has recently developed two behavioral tests that can be used to uncover visual system specific mutations in zebrafish. One test enables us to isolate recessive visual system mutations in larval fish, whereas the second test is used to isolate dominant visual system mutations in adult fish. In this talk, I shall describe several of the mutants we have isolated and discuss their relevance for understanding visual mechanisms.