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Notch is a transmembrane receptor that binds cognate membrane bound ligands on a neighboring cell. Upon binding, Notch is cleaved, forming an intracellular domain (NICD) that translocates to the nucleus where it forms a complex with the Suppressor of hairless [Su(H)] protein. The NICD/Su(H) complex directly activates the expression of target genes which includes members of the hairy family (HES) of transcriptional repressors. HES factors block alternative cell fates, usually by repressing expression of genes normally expressed in the ligand bearing cell. The end result is that the two cells pictured above will become different cell types. en