Ihh

Ihh, or Indian hedgehog, is a secreted signaling protein encoded by the IHH gene, a member of the vertebrate hedgehog family that coordinates embryonic development and tissue patterning. In humans, Ihh plays a key role in the regulation of bone growth and skeletal formation.

Ihh functions as part of the Hedgehog signaling pathway. In the absence of Hedgehog ligands, the receptor PTCH1 inhibits the activity of Smoothened (SMO). When Ihh binds to PTCH1, this inhibition is relieved, SMO becomes active, and intracellular GLI transcription factors are activated to drive Hedgehog target gene expression. This signaling cascade is tightly regulated and interacts with other pathways to influence cell fate and growth.

Expression and role in skeletal development: Ihh is produced by prehypertrophic and early hypertrophic chondrocytes in developing long bones. It governs endochondral ossification by promoting chondrocyte proliferation and delaying hypertrophic differentiation. Ihh also participates in the feedback loop with parathyroid hormone-related protein (PTHrP), helping to coordinate growth plate function and longitudinal bone growth.

Clinical significance: Mutations in IHH can cause skeletal dysplasias, most notably brachydactyly type A1, which involves shortened or missing bones in the digits. The spectrum of phenotypes can vary with the specific mutation, reflecting Ihh’s crucial role in cartilage and bone development.

Research and therapeutic context: The Ihh signaling pathway remains a focus of skeletal biology and growth-related research. While Hedgehog pathway modulators are used clinically in oncology, ongoing studies explore how targeted modulation of Ihh signaling might influence bone growth, repair, and related disorders.