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The Hedgehog Pathway

Summary

In its resting state, the Patched receptor prevents activation of the Hedgehog pathway by inhibiting Smoothened. When secreted Hedgehog ligand binds to and inactivates Patched, that results in activation of Smoothened. This triggers a cascade of signaling events that result in gene transcription of Hedgehog target genes through the Gli family of transcription factors.¹ Direct targets of Hedgehog pathway activity include genes involved in cell proliferation, development, and tissue maintenance.^2-4

The Hedgehog pathway is regulated at different levels within the pathway. At the cell surface, the negative regulator Hhip competes with Patched for Hedgehog ligand binding.^5,6 Positive regulators Cdo, Boc, and Gas1 enhance the binding of Hedgehog ligands to Patched.^7-9 Inside the cell, there is regulation of the transport of Hedgehog pathway components to the cilium, and Suppressor of fused (Sufu) protein is a negative regulator of Gli transcriptional activity.^10-12 Click one of the links below to learn more.

• The Hedgehog pathway in its resting state
• Activation of the Hedgehog pathway
• Regulation of the Hedgehog pathway