The Notch signaling pathway is named after an X-linked, dominant mutation that was first isolated in Drosophila, which caused irregular tissue loss (notches) at the tips of the wing blades (Mohr 1919). However, it is now known that Notch signaling regulates multiple aspects of invertebrate and vertebrate development in a number of cell types including cardiac, endocrine and immune cells (Fortini 2009). Notch signaling remains active in the adult where it is involved in processes ranging from the maintenance of stem cell populations and differentiation to synaptic plasticity and memory formation (Kopan and Llagan 2009). Perturbations in Notch signaling have been implicated in cancer biology and in neurological disease.
There are four mammalian Notch receptors (Notch 1, Notch2, Notch3, and Notch4), two in C. elegans (LIN-12 and GLP-1) and one in Drosophil (Notch), but the basic signaling paradigm is common across species (Fiúza and Arias 2007; Kopan and Llagan 2009). Notch receptors are large single pass, glycosylated, transmembrane proteins that are characterized by numerous (over thirty) extracellular epider