THE DROSOPHILA NUMB PROTEIN INHIBITS SIGNALING OF THE NOTCH RECEPTOR DURING CELL-CELL INTERACTION IN SENSORY ORGAN LINEAGE

Specification of unequal daughter cell fates in the Drosophila externa l sense organ lineage requires asymmetric localization of the intrinsi c determinant Numb as well as cell-cell interactions mediated by the D elta ligand and Notch receptor. Previous genetic studies indicated tha t numb acts upstream of Notch, and biochemical studies revealed that N umb can bind Notch. For a functional assay of the action of Numb on No tch signaling, we expressed these proteins in cultured Drosophila cell s and used nuclear translocation of Suppressor of Hairless [Su(H)] as a reporter for Notch activity. We found that Numb interfered with the ability of Notch to cause nuclear translocation of Su(H); both the C-t erminal half of the phosphotyrosine binding domain and the C terminus of Numb are required to inhibit Notch. Overexpression of Numb during w ing development, which is sensitive to Notch dosage, revealed that Num b is also able to inhibit the Notch receptor in vivo. In the external sense organ lineage, the phosphotyrosine binding domain of Numb was fo und to be essential for the function but not for asymmetric localizati on of Numb. Our results suggest that Numb determines daughter cell fat es in the external sense organ lineage by inhibiting Notch signaling.