Notch
Definition
Notch is a highly conserved cell-to-cell signaling pathway that regulates cell fate decisions, proliferation, differentiation, and apoptosis across metazoan development and adult tissue homeostasis. The pathway operates through direct contact between neighboring cells: a transmembrane Notch receptor on one cell binds to transmembrane ligands (Delta, Jagged/Serrate family) on an adjacent cell, triggering proteolytic cleavage by γ-secretase. This releases the Notch intracellular domain (NICD), which translocates to the nucleus and activates transcription of target genes including HES and HEY family members. Dysregulation of Notch signaling is implicated in numerous cancers, developmental disorders, and cardiovascular diseases, making it a critical therapeutic target.
Visualize Notch in Nodes Bio
Researchers can map Notch pathway networks showing receptor-ligand interactions, downstream transcriptional cascades, and crosstalk with other signaling pathways like Wnt and Hedgehog. Network visualization reveals how Notch components interact with oncogenes in cancer contexts, identifies feedback loops regulating lateral inhibition, and highlights potential drug targets by analyzing pathway bottlenecks and hub proteins within the signaling cascade.
Visualization Ideas:
- Notch receptor-ligand binding networks showing Delta/Jagged family interactions across cell boundaries
- Transcriptional regulatory networks mapping NICD nuclear translocation to HES/HEY target gene activation
- Multi-pathway crosstalk networks illustrating Notch interactions with Wnt, Hedgehog, and growth factor signaling cascades
Example Use Case
A cancer biology team investigating T-cell acute lymphoblastic leukemia (T-ALL) uses network analysis to map aberrant Notch1 signaling. They visualize how activating mutations in Notch1 create sustained pathway activation, identifying downstream targets like MYC and mTOR that drive proliferation. By overlaying drug interaction data, they discover that combining γ-secretase inhibitors with PI3K-AKT pathway inhibitors creates synthetic lethality. The network reveals compensatory feedback mechanisms explaining resistance patterns observed in clinical trials.