Ebi modulates wing growth by ubiquitin-dependent downregulation of crumbs in Drosophila

Notch signaling at the dorsoventral (DV) boundary is essential for patterning and growth of wings in Drosophila. The WD40 domain protein Ebi has been implicated in the regulation of Notch signaling at the DV boundary. Here we show that Ebi regulates wing growth by antagonizing the function of the transmembrane protein Crumbs (Crb). Ebi physically binds to the extracellular domain of Crb (Crb^ext), and this interaction is specifically mediated by WD40 repeats 7-8 of Ebi and a laminin G domain of Crb^ext. Wing notching resulting from reduced levels of Ebi is suppressed by decreasing the Crb function. Consistent with this antagonistic genetic relationship, Ebi knockdown in the DV boundary elevates the Crb protein level. Furthermore, we show that Ebi is required for downregulation of Crb by ubiquitylation. Taken together, we propose that the interplay of Crb expression in the DV boundary and ubiquitin-dependent Crb downregulation by Ebi provides a mechanism for the maintenance of Notch signaling during wing development.