Hedgehog
Definition
Hedgehog signaling is a highly conserved developmental pathway that regulates cell differentiation, proliferation, and tissue patterning during embryogenesis and adult tissue homeostasis. The pathway is initiated when Hedgehog ligands (Sonic, Indian, or Desert Hedgehog) bind to the Patched (PTCH) receptor, relieving its inhibition of Smoothened (SMO). Activated SMO triggers a signaling cascade that prevents proteolytic processing of GLI transcription factors, allowing them to translocate to the nucleus and activate target gene expression. Aberrant Hedgehog signaling is implicated in various cancers, including basal cell carcinoma and medulloblastoma, making it a critical therapeutic target. The pathway's complexity involves multiple feedback loops and crosstalk with other signaling networks.
Visualize Hedgehog in Nodes Bio
Researchers can map Hedgehog pathway components and their interactions in network graphs to identify key regulatory nodes and feedback mechanisms. Nodes Bio enables visualization of ligand-receptor binding, downstream effector cascades, and crosstalk with WNT, TGF-β, and Notch pathways. Users can overlay expression data to identify pathway dysregulation patterns across cancer subtypes or developmental stages, revealing potential therapeutic intervention points.
Visualization Ideas:
- Hedgehog ligand-receptor interaction networks showing PTCH-SMO dynamics
- GLI transcription factor regulatory networks with target gene connections
- Cross-pathway networks mapping Hedgehog crosstalk with WNT, Notch, and TGF-β signaling
Example Use Case
A pharmaceutical team investigating resistance mechanisms to SMO inhibitors in medulloblastoma patients uses network analysis to map Hedgehog pathway alterations. By visualizing protein-protein interactions and gene expression changes in resistant versus sensitive tumors, they discover that GLI2 amplification and non-canonical pathway activation through PI3K/AKT bypass SMO blockade. The network reveals that dual inhibition of SMO and PI3K could overcome resistance, leading to a combination therapy clinical trial design.