Notch signaling genes

Notch intercellular signaling is essential to cell fate decisions during differentiation, especially in stem cells and progenitor cells. It is also involved in controlling proliferation, survival, and homeostasis in many cell types. Notch signaling genes are targets for pathogenic mutations, including those associated with cancer. In the skeletal muscle lineage, Notch signaling is implicated in the quiescence of postnatal muscle stem cells (satellite cells), the proliferation of myoblasts (Mb)—which are activated satellite cells—and the transient inhibition of terminal differentiation of Mb into multinucleated myotubes (Mt). Among other cell types that Notch signaling guides into selfrenewal or differentiation pathways are cardiac and neural stem cells. In canonical Notch signaling, the Notch receptor protein (NOTCH1, NOTCH2, NOTCH3, or NOTCH4 in human cells) spans the cell membrane as a heterodimer of the proteolytically cleaved precursor protein. The heterodimer is activated upon interaction with a Notch ligand (DLL1, DLL3, DLL4, JAG1, or JAG2) on the membrane of an adjacent cell and then cleaved to yield a NOTCH protein fragment that migrates to the nucleus. In the nucleus, this fragmented, active form of NOTCH1 or NOTCH2 converts a transcription regulatory protein (RBPJ) from being a repressor to being an activator, thereby inducing expression of key genes. Different Notch receptors and ligands play different cell-type specific roles. For example, NOTCH1, but not NOTCH2 or NOTCH3, is implicated in stimulating proliferation of porcine muscle satellite cells, even though