Nature Chem. Bio. doi:10.1038/nchembio.190 (2009)

Michael Tsang and colleagues at the University of Pittsburgh, Pennsylvania, wanted to find small-molecule modulators of the fibroblast growth factor (FGF) pathway, which is central to embryonic development. They screened chemicals in zebrafish that had been engineered to glow when FGF was active. One chemical known as BCI supercharged the glow, indicating it was boosting FGF activity.

Further study revealed that BCI blocks the activity of dual-specificity phosphatase 6 (Dusp6), an FGF feedback regulator, thereby stopping it from impairing FGF and resulting in the extra glow. Compared with untreated zebrafish embryos, BCI-treated embryos had more cardiac progenitor cells — which eventually give rise to the heart — but fewer of the cells that go on to line blood vessels and form blood cells. The results, say Tsang's team, demonstrate the utility of zebrafish in chemical screens in vivo.