Figure 1

Model of the canonical Hedgehog signalling pathway in mammals. (A) In the absence of Hedgehog (Hh) ligand, the receptor Patched (Ptch) inhibits the activation of Smoothened (Smo) by preventing its surface translocation into the cilium. The Glioma-associated (GLI) proteins are phosphorylated and processed to truncated repressor forms. This inactive GLI protein complex functions as a transcriptional repressor of Hh target gene expression. Suppressor of fused (SUFU) inhibits GLI1 and GLI2 from entering the nucleus by sequestering the complex to the microtubules and represses transcription. (B) The binding of Hh ligands to Ptch releases the repression on Smo, leading to the movement of Smo from an intracellular vesicle to the tip of the primary cilium. Activated GLI proteins then translocate to the nucleus and promote the transcription of target genes. To note, Hh ligand binding is regulated by cell surface proteins: Hh-interacting protein (HHIP) and heparan sulfate proteoglycans (HSPGs) compete with the Hh-binding while GAS1 (Growth arrest-specific gene), Cdo (Commodo) and Boc (Brother of Commodo) proteins facilitate Hh-binding to Ptch.