Activation of the Hedgehog pathway

Hedgehog pathway signaling is initiated upon binding of the Hedgehog ligand to the PTCH receptor. This leads to PTCH internalization and degradation, and the removal of its inhibitory effect over SMO.¹ Activated SMO then moves from an intracellular vesicle to the cell membrane of the cilium, where it activates the Gli family of transcription factors, including Gli2 and Gli3.¹⁸ Activated Gli proteins enter the nucleus and initiate the transcription of target genes.¹⁹

Direct targets of Hedgehog pathway activity are the following 3 genes found in the pathway itself: Gli1, PTCH1, and Hhip.^2,3,20 Other confirmed direct targets include genes involved in cell proliferation, development, and tissue maintenance.^2-4,21,22