rhythms, flies have become an excellent organism for identifying genes involved directly in behavior. Some of the major discoveries of genes controlling specific behavior traits have been accomplished in Drosophila. For example, the recent identification of genes controlling circadean rhythms in mammals (Takahashi 1995) owes its origin to the genetic screens that revealed the per locus in Drosophila (Konopka and Benzer 1971). Subsequent Drosophila screens have disclosed other components of the molecular clock—such as Timeless, Cycle, and Clock—which are also conserved in other organisms for photo-period regulation. Similarly, genetic screens in Drosophila have identified the mutants, such as Dunce, Turnip, Cabbage, Amnesiac, and Rutabaga that affect associative learning (Dubnau and Tully 1998). These genes have been shown to be part of the adenyl cyclase pathway.
Possibly the most elaborate behavioral patterns of Drosophila involve courtship behavior, which includes a series of species-specific activities essential for successful mating (Hall 1998). Starting from these successful pioneering studies, many of which were initiated in the laboratory of S. Benzer, Drosophila has become a useful organism for exploring the genetic basis for alcoholism (Bellen 1998), susceptibility to drugs (McClung and Hirsh 1999), aging (Lin et al. 1998), and other neurobehavioral traits. Because of the simplicity of its life cycle and rearing needs, the fly will continue to be an important first step in the identification of genes controlling a wide variety of behaviors. It should also be extremely useful for detecting deleterious effect of toxicants on specific behaviors, and as described above, the tests could be done on sensitized strains.
The zebrafish is an appropriate model organism in which to test potentially toxic chemicals for several reasons. First, the zebrafish is a vertebrate and therefore of more direct relevance to the role of pathways in development of vertebrate-specific tissues and organs, such as the neural crest (Kelsh et al.1996; Schilling et al. 1996) and parts of the heart (Stainier et al. 1996), which are affected in many congenital anomalies. Second, chemicals can be added directly to the water (Stainier and Fishman 1992). Third, the zebrafish embryo is transparent, so tissue and organ development can readily be assayed. Viable, preferably dominant, mutations would be needed as the sensitized target to make such screens achievable on a large scale. Some viable pigmentation mutations have different heterozygous and homozygous phenotypes, indicating a dose responsiveness to the defect (Haffter et al.1996), and therefore are candidates, but these mutations have not been cloned, so the affected pathways remain to be determined. The potential is great for devising assays for chemical effects on development.
The zebrafish embryo has been used for toxicological assays (Ensenbach and Nagel 1995, 1997; Henry et al. 1997; Mizell and Romig 1997); however, it has not been developed for sensitized assays. Such assays are now feasible and would