Chemical discovery and global gene expression analysis in zebrafish

Abstract

The zebrafish (Danio rerio) provides an excellent model for studying vertebrate development and human disease because of its ex utero, optically transparent embryogenesis and amenability to in vivo manipulation. The rapid embryonic developmental cycle, large clutch sizes and ease of maintenance at large numbers also add to the appeal of this species. Considerable genomic data has recently become publicly available that is aiding the construction of zebrafish microarrays, thus permitting global gene expression analysis. The zebrafish is also suitable for chemical genomics, in part as a result of the permeability of its embryos to small molecules and consequent avoidance of external confounding maternal effects. Finally, there is increasing characterization and analysis of zebrafish models of human disease. Thus, the zebrafish offers a high-quality, high-throughput bioassay tool for determining the biological effect of small molecules as well as for dissecting biological pathways.

Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish

“…Such inhibitors, in effect, allow one to easily perform a "conditional knockout" experiment, and thereby uncover novel and specific functions of the targeted proteins. Indeed, use of small cell permeable molecules to perturb function of specific proteins in zebrafish is emerging as an exciting area of chemical genomics (Pichler et al, 2003).…”

Zebrafish: At the Nexus of Functional and Chemical Genomics

“…An assay rnust be applicable (eventuaHy) to a high throughput process, but offer the abiJity to answer potentially cOlnplex questions related to the disease process. It should nOl go unnoticed lhat a high throughput approach lends itsel f to screening thousands of snla]) 1l10)ecules, wh ich has received recent attention with respect to the use of zebrafish elnbryos (Pichler et al., 2003;Goldsrllith, 2004;Love et aJ., 2004;Peterson, 2004;Peterson et al, 2004). The principal outcotne to these studies should be to provide high biological value to the disease being studied, while at the saIne thue achieving a throughput thal serves as a drug discovery platfoTill.…”

“…This approach has been reviewed by the author's laboratory, which can falJ into the area of chemical genoillics (Pichler et al, 2003;Love et al2 004). This interest has also initiated the development of several zebrafish-based drug developnlent conlpanies (Pichler et al, 2004b).…”

In vivo tracking of T cell development, ablation, and engraftment in transgenic zebrafish

“…Such genetic approaches have been used successfully to identify genes involved in patterning, regeneration, and the development of organs, including heart, eye, and blood (4,5). Additionally, small-molecule-based screens in the zebrafish have identified chemicals that perturb normal development (6,7), and drug screens have been proposed to identify compounds that suppress cancer-associated phenotypes (8)(9)(10).…”