# 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.

## Sources

- Bray SJ. (2006). Notch signalling: a simple pathway becomes complex. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/nrm2009
- Gridley T. (2010). Notch signaling in the vasculature. Current Topics in Developmental Biology. https://doi.org/10.1016/S0070-2153(10)92009-7

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