Advances in zebrafish chemical screening technologies

Abstract

Due to several inherent advantages, zebrafish are being utilized in increasingly sophisticated screens to assess the physiological effects of chemical compounds directly in living vertebrate organisms. Diverse screening platforms showcase these advantages. Morphological assays encompassing basic qualitative observations to automated imaging, manipulation, and data-processing systems provide whole organism to subcellular levels of detail. Behavioral screens extend chemical screening to the level of complex systems. In addition, zebrafish-based disease models provide a means of identifying new potential therapeutic strategies. Automated systems for handling/sorting, high-resolution imaging and quantitative data collection have significantly increased throughput in recent years. These advances will make it easier to capture multiple streams of information from a given sample and facilitate integration of zebrafish at the earliest stages of the drug-discovery process, providing potential solutions to current drug-development bottlenecks. Here we outline advances that have been made within the growing field of zebrafish chemical screening.

Figure 1. Expression of fluorescent reporters in zebrafish larvae arrayed in a single well of a 96-well plate

Three transgenic larvae (Tg[ins:PhiYFP-Eco. NfsB,sst2:TagRFP]lmc01 at 4 days post-fertilization) co-expressing PhiYFP (Evrogen) and nitroreductase in beta cells of the pancreas (arrow) are shown [3]; for comparison a single nontransgenic larva is included at the bottom. At this stage larvae naturally settle into a lateral view that is highly amenable to imaging and/or plate reader-based quantification.