Abstract
In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads, and explore new applications for known drugs. Here, we discuss some of the advantages of using zebrafish in chemical biology, and describe some important and creative examples of small molecule screening, drug discovery and target identification.
Highlights
In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology
The zebrafish system has been especially powerful in the identification of developmental phenotypes, caused by N-ethyl N-nitrosourea (ENU) and insertional mutagenesis, and many of the underlying genetic mutations have been identified [4,5,6,7,8]
Ten years after the first small molecule screen in zebrafish, we have examples of how small molecules can lead to fundamental insight into developmental and behavioural processes, to new clinical strategies, and to understanding of the action of currently used drugs
Summary
The combination of genetic and developmental features places zebrafish small molecule screening at the cutting edge of chemical biology. Ten years after the first small molecule screen in zebrafish, we have examples of how small molecules can lead to fundamental insight into developmental and behavioural processes, to new clinical strategies, and to understanding of the action of currently used drugs. We are only just beginning to understand how small molecules act within living animals and the transparent nature of the zebrafish embryo may facilitate future visualization and understanding of how chemicals act upon targets within cells. Sharing of chemical libraries between zebrafish researchers with diverse biological interests should lead to an unprecedented wealth of new insight into chemical biology within a whole animal system [95].
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