Hedgehog (Hh) is a secreted morphogen that regulates developmental processes in vertebrates including limb bud formation, neural tube patterning, cell growth and differentiation (reviewed in Hui and Angers, 2011). Hh signaling also contributes to stem cell homeostasis in adult tissues. Downregulation of Hh signaling can lead to neonatal abnormalities, while upregulation of signaling is associated with the development of various cancers (Beachy et al, 2004; Jiang and Hui, 2008; Hui and Angers, 2011).
Hh signaling is switched between 'off' and an 'on' states to differentially regulate an intracellular signaling cascade that targets the Gli transcription factors. In the absence of Hh ligand, cytosolic Gli proteins are cleaved to yield a truncated form that translocates into the nucleus and represses target gene transcription. Binding of Hh to the Patched (PTC) receptor on the cell surface stabilizes the Gli proteins in their full-length transcriptional activator form, stimulating Hh-dependent gene expression (reviewed in Hui and Angers, 2011; Briscoe and Therond, 2013).