Figure 1.

Flies, sheep, corn lilies, cyclops and Sonic the Hedgehog point the way to novel cancer therapeutics. Early genetic studies in Drosophila (a) described the role of the HH pathway in development and later this was extended to mammals. Mutations in the HH gene cause holoprosencephaly (cyclops-like phenotype) in mice, sheep (b), humans and mythical beasts (c). The same phenotype arises in lambs born to ewes that ingest the corn lily plant (V. californicum) (d) in the first trimester. This was the clue that ultimately led to the identification of small molecule inhibitors of the HH pathway. The mammalian HH gene family includes SHH, a name inspired by the eponymous video game character designed by Sega Inc. (e). Illustrations by T. Curran.