Figure 2.

Hedgehog signaling at the primary cilium in vertebrates. (A) In the unstimulated state, Ptc1 sits in the cilium membrane and represses and excludes Smoothened (Smo) from the cilium. Gli transcription factors are sequestered and suppressed by Suppressor of Fused (SuFu) at the tip of the primary cilium. (B) In the stimulated state, upon binding of Shh to Ptc1, the repression of Smo by Ptc1 is relieved, allowing Smo to enter the cilium and Ptc1 to leave the cilium. This then allows Smo to repress SuFu, relieving repression of Gli at the tip of the cilium. Gli is thus freed to be post-translationally modified to form Gli activator form (GliA), which is transported out of the cilium to the nucleus to activate expression of downstream target genes.