Deconstructing the hedgehog pathway in development and disease

The Hedgehog (Hh) family of secreted signaling proteins is a master regulator of cell fate determination in metazoans, contributing to both pattern formation during embryonic development and postembryonic tissue homeostasis. In a universally used mode of action, graded distribution of Hh protein induces differential cell fate in a dose-dependent manner in cells that receive Hh. Though much of this pathway has been elucidated from genetically based studies in model organisms, such as Drosophila and mice, the importance of Hh-mediated signaling in humans is clearly evident from malformations and a broad range of cancers that arise when the pathway is corrupted.