Agonizing Hedgehog

It is a rare treat when a drug discovery program teaches us something about the biology of the process that it attempts to modulate. The paper by Maria Frank-Kamenetsky and colleagues in this issue of theJournal of Biology[1] presents a compelling example of how the search for therapeutics can provide powerful experimental tools and insights into fundamental biology, blurring the distinction between applied and basic research. By characterizing a small group of chemically similar agonists of theHedgehogsignaling pathway, Frank-Kamenetskyet al. have been able to propose a new model for how theSmoothenedcomponent of the Hedgehog-receptor complex works, and to hint at the existence of natural-ligand agonists of the Hedgehog signaling pathway (see'The bottom line'box for a summary of their work).