Sonic hedgehog protein

SHH gradient and Gli activity in the vertebrate neural tube.

Sonic hedgehog protein (SHH) is a protein that in humans is encoded by the SHH gene. It is a member of the hedgehog signaling pathway and plays a critical role in the development of the embryo in many animals, including humans. The protein is named after the Sonic the Hedgehog video game character due to its role in regulating the growth and division of cells, which can lead to the formation of digits in limbs and the organization of the brain.

Function

Sonic hedgehog protein is a signaling molecule that is involved in the patterning of the embryonic structures, including the central nervous system, the vertebrate limbs, and the teeth. It functions by binding to the Patched-1 (PTCH1) receptor, which in the absence of SHH inhibits the activity of the Smoothened (SMO) protein. When SHH binds to PTCH1, SMO is released from this inhibition and initiates a signaling cascade that leads to the activation of GLI transcription factors, which then enter the nucleus and affect the expression of target genes.

Genetics

The SHH gene is located on the long (q) arm of chromosome 7 at position 36, specifically 7q36. It consists of three exons and encodes the Sonic hedgehog protein. Mutations in the SHH gene have been linked to several developmental disorders, including holoprosencephaly, a condition characterized by the failure of the forebrain to divide into two hemispheres, and polydactyly, the presence of extra fingers or toes.

Clinical Significance

Beyond its role in development, aberrant SHH signaling has been implicated in the pathogenesis of various types of cancer, including basal cell carcinoma, medulloblastoma, and others. Inhibitors of the SHH pathway are being explored as potential therapeutic agents in these conditions.

Evolution

The hedgehog gene family, to which SHH belongs, is highly conserved across a wide range of species, indicating its fundamental role in animal development. The family includes three members in vertebrates: Sonic hedgehog (SHH), Indian hedgehog (IHH), and Desert hedgehog (DHH), each with distinct but overlapping patterns of expression and functions.

See Also

• Hedgehog signaling pathway
• Gene
• Protein
• Embryonic development
• Mutation