Hedgehog signaling pathway

Hedgehog signaling pathway is a key cell signaling system that plays a crucial role in the development of organisms across the animal kingdom. It is named after the Hedgehog (Hh) gene, which was first identified in the fruit fly species Drosophila melanogaster. The pathway is involved in the regulation of cell growth, cell differentiation, and the formation of the body plan.

Function

The Hedgehog signaling pathway is activated when a Hedgehog protein binds to the Patched (Ptc) receptor on the cell surface. In the absence of Hedgehog, Patched inhibits another protein called Smoothened (Smo). When Hedgehog binds to Patched, this inhibition is relieved, allowing Smoothened to activate a series of downstream signaling events. These events ultimately lead to the activation of Gli transcription factors, which regulate the expression of target genes.

Role in Development

During embryonic development, the Hedgehog signaling pathway helps to establish the body plan. It does this by determining the pattern of tissue growth and the differentiation of cells into different types. For example, in the developing vertebrate limb, Hedgehog signaling is involved in determining the pattern of digit formation.

Role in Disease

Abnormalities in the Hedgehog signaling pathway can lead to a variety of diseases. Overactivation of the pathway can lead to cancer, including basal cell carcinoma, the most common type of skin cancer, and medulloblastoma, a type of brain cancer. Mutations in components of the pathway can also cause congenital disorders, such as Holoprosencephaly, a severe brain malformation, and Gorlin syndrome, a condition characterized by the development of multiple basal cell carcinomas and other abnormalities.

Therapeutic Target

Given its role in disease, the Hedgehog signaling pathway is a target for therapeutic intervention. Several drugs that inhibit the pathway are currently in clinical use or under development. These include vismodegib and sonidegib, which are used to treat basal cell carcinoma.

See Also

• Wnt signaling pathway
• Notch signaling pathway
• TGF beta signaling pathway

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