Fig. 2

Sonic hedgehog signaling pathway. In the absence of sonic hedgehog ligand (Shh), the surface receptor Patched1 (PTCH1) inhibits Smoothened (SMO), resulting in sequestration of Gli1 in the cytosol by Suppressor of fused (SUFU). Binding of Shh to PTCH1 abolishes constitutive inhibition of SMO by PTCH1, leading to liberation of Gli1 from SUFU. Released Gli1, then, translocates to the nucleus, where it promotes gene expression. Sonic Hedgehog inhibitors IPI-926 (Saridegib) and Vismodegib block SMO activity