Sonic hedgehog (Shh) is a mammalian hedgehog (Hh) pathway ligand that mediates epithelial–mesenchymal interactions in lung development. Loss of Shh function results in severe lung defects associated with failure of branching morphogenesis. However, the role of Shh in regeneration and carcinogenesis of airway epithelium is unknown. In the March 5 advanced online
Watkins et al. studied a murine model of acute airway repair and observed extensive activation of the Hh pathway within the airway epithelium during repair. In addition, they found a similar pattern of Hh signaling in a subset of small-cell lung cancer (SCLC) cells with primitive neuroendocrine features. These tumors maintained their malignant phenotype in vitro and...