The New Age of Chemical Screening in Zebrafish

The zebrafish embryo is particularly well suited for screening small molecules for their effects on development. Zebrafish absorb many compounds readily in the first days of life and this facilitates an analysis of phenotypes. Suppressor screens are possible to look for chemicals that can alleviate a variety of disease states in the zebrafish. To date, over 10 zebrafish chemical screens have been reported in the literature, resulting in identification of a variety of pathways regulating organogenesis and organ function. A few of those chemicals are starting to make it into the clinic. For instance, dimethyl prostaglandin E2 was found in a screen for inducing stem cells in zebrafish and has now been placed into a clinical trial for leukemia and cord blood transplantation. This demonstrates that zebrafish can have significant impact on our understanding of development of disease through chemical genetics.

In this issue, several new chemical screens and chemical biological studies are described. The articles have significant breadth, from xenobiotic metabolism to toxicology to understanding regeneration. These articles reflect a growing community of researchers interested in doing chemical screens in zebrafish. At a recent meeting in Rome, over 150 investigators were present for an interim lunch session on chemical screening in zebrafish. Recently, we (along with Liz Patton) have set up a USTREAM videoconference in which 150 people were online simultaneously looking for information about chemical screening in zebrafish. There clearly is an appetite for applying chemical biology approaches in the zebrafish system.

Future successes in this field will be accelerated by increasing the throughput of our chemical screening and by developing better approaches for following up on the hits that come from screening. We also need to stay focused on screening for relevant phenotypes that affect early development and disease and improve our ability to screen in adults. These advances will ultimately allow the zebrafish community to have a greater impact on biology and medicine. The articles in this issue move us closer to that goal. We are very excited by this issue and hope you will enjoy reading it.