Notch signaling

Notch signaling is a cell-to-cell communication system that decides cell fates and keeps tissues balanced. It works only by direct contact between touching cells. Here is the relay. A ligand (Delta-like or Jagged) on one cell binds a Notch receptor (NOTCH1 through 4) on the neighbor. That triggers two cuts in a row: first by ADAM proteases (the S2 cut), then by the γ-secretase complex (the S3 cut). The cuts free the Notch intracellular domain (NICD). NICD then travels to the nucleus and switches on genes (via the CSL/RBPJ complex). Notch regulates many things. It keeps your muscle stem cells dormant, guides muscle and nerve regeneration, and shapes T-cell development. Its activity falls with age in several tissues, which hurts repair. And dysregulation in either direction, too much or too little, is tied to pathological aging and cancer.

Last reviewed: June 22, 2026

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