The Notch signalling pathway appears to be ubiquitous in virtually all cell-cell contacts in all metazoan animals, and is best known and most throughout studied in Drosophila melanogaster. In this species the Notch signalling pathway regulates, with both positive and negative signals, the differentiation of at least central and peripheral nervous system and eye, wing disc, oogenesis, segmental appendages such as antennae and legs, and muscles, through lateral inhibition or induction. In general, the pathway works as follows: Notch is most likely a dimeric transmembrane receptor at the cell surface, where it is activated by its ligands Serrate and or Delta from the neighbouring cell Fringe, discriminating between the two ligands. Then, the receptor is cleaved by a proteolytic mechanism in which Presenilin plays an important role, and the intracellular domain is transferred to the nucleus, where it, together with the Suppressor of Hairless protein, constitutes a transcription factor which activates the Notch target genes, mainly located in the Enhancer of split complex. These target genes then encode repressor proteins.