Notch signaling targets the Wingless responsiveness of a Ubx visceral mesoderm enhancer in Drosophila

Background: Members of the Notch family of receptors mediate a process know n as lateral inhibition that plays a prominent role in the suppression of c ell fates during development. This function is triggered by a ligand, Delta , and is implemented by the release of the intracellular domain of Notch fr om the membrane and by its interaction with the protein Suppressor of Hairl ess [Su(H)] in the nucleus. There is evidence that Notch can also signal in dependently of Su(H). In particular, in Drosophila, there is evidence that a Su(H)-independent activity of Notch is associated with Wingless signaling , Results: We report that Ubx(VM)B, a visceral mesoderm-specific enhancer of the Ubx gene of Drosophila, is sensitive to Notch signaling. In the absence of Notch, but not of Su(H), the enhancer becomes activated earlier and ove r a wider domain than in the wild type. Furthermore, the removal of Notch r educes the requirement for Disheveled-mediated Wingless signaling to activa te this enhancer. This response to Notch is likely to be mediated by the dT cf binding sites in the Ubx(VM)B enhancer. Conclusions: Our results show that, in Drosophila, an activity of Notch tha t is likely to be independent of Su(H) inhibits Wingless signaling on Ubx(V M)B. A possible target of this activity is dTcf. As dTcf has been shown to be capable of repressing Wingless targets, our results suggest that this re pressive activity may be regulated by Notch. Finally, we suggest that Wingl ess signaling is composed of two steps, a down-regulation of a Su(H)-indepe ndent Notch activity that modulates the activity of dTcf and a canonical Wi ngless signaling event that regulates the activity of Armadillo and its int eraction with dTcf.