Two different activities of Suppressor of Hairless during wing developmentin Drosophila

The Notch pathway plays a crucial and universal role in the assignation of cell fates during development. In Drosophila, Notch is a transmembrane prot ein that acts as a receptor of two ligands Serrate and Delta. The current m odel of Notch signal transduction proposes that Notch is activated upon bin ding its ligands and that this leads to the cleavage and release of its int racellular domain (also called Nintra). Nintra translocates to the nucleus where it forms a dimeric transcription activator with the Su(H) protein. In contrast with this activation model, experiments with the vertebrate homol ogue of Su(H), CBF1, suggest that, in vertebrates, Nintra converts CBF1 fro m a repressor into an activator. Here we have assessed the role of Su(H) in Notch signalling during the development of the wing of Drosophila, Our res ults show that, during this process, Su(H) can activate the expression of s ome Notch target genes and that it can do so without the activation of the Notch pathway or the presence of Nintra. In contrast, the activation of oth er Notch target genes requires both Su(H) and Nintra, and, in the absence o f Nintra, Su(H) acts as a repressor, We also find that the Hairless protein interacts with Notch signalling during wing development and inhibits the a ctivity of Su(H), Our results suggest that, in Drosophila, the activation o f Su(H) by Notch involve the release of Su(H) from an inhibitory complex, w hich contains the Hairless protein. After its release Su(H) can activate ge ne expression in absence of Nintra.