Fig. 1. The Hedgehog pathway in Drosophila and vertebrates. The Hedgehog (Hh) pathway in Drosophila (A,B) and in vertebrates (C,D) in the absence (A,C) or presence (B,D) of the Hh ligand. (A) In the absence of Hh, Ptc prevents the cell-surface localization of Smo, and Ci forms a complex with Cos2, Fu and Sufu, which targets Ci for proteolytic processing into the repressor form (Ci^R). (B) In the presence of high levels of Hh ligand, Ptc inhibition is relieved; Smo accumulates at the plasma membrane and forms a complex with Cos2 and Fu through its C-terminal tail; Ci is activated. (C) In the absence of Hh, Ptch1 prevents the accumulation of Smo in cilia, possibly through the action of a small molecule. Gli3 is processed into a repressor form (Gli3^R) in a cilia-dependent manner. The activation of all Gli proteins is inhibited by Sufu, Iguana (for zebrafish) and probably Cos2. (D) In the presence of high levels of Hh ligand, Ptch1 inhibition is relieved; Smo is targeted to cilia and activates Gli proteins in a cilia-dependent manner. Gli3 processing is also inhibited. p, phosphorylation; PKA, protein kinase A.