Regulating the Notch pathway in embryonic, adult and old stem cells.

The Notch pathway represents a highly conserved signaling network, which is critical to both embryonic skeletal muscle formation and regeneration in the adult. In addition to skeletal muscle, Notch also regulates the formation and maintenance of various organ systems, such as brain, blood and intestine, in evolutionary distinct vertebrate and invertebrate species. The Notch network 'cross talks' with all other key cell-fate determinants, such as the Wnt (Wingless), TGF-beta/BMP, Hh and RTK/Ras pathways. Hence, modulating the intensity of Notch resonates through multiple regulatory circuitries, and exerts profound effects on cell behaviour. Therefore, various approaches to the targeted manipulation of Notch have been developed (e.g. genetic constructs, antibodies, RNA interference, receptor decoys and gamma-secretase inhibitors). These tools might be used to broaden our understanding of this pathway in regulating responses of embryonic and adult stem cell subsets, and to develop therapeutic approaches against Notch-based diseases (e.g. Alzheimer's, Alagille Syndrome, various cancers and other disease states).