Identification of novel Ras-cooperating oncogenes in Drosophila melanogaster: a RhoGEF/Rho-family/JNK pathway is a central driver of tumorigenesis.
Although the formation and maintenance of epithelial tubes are essential for the viability of multicellular organisms, our understanding of the molecular and cellular events coordinating tubulogenesis is relatively limited. Here, we focus on the activities of Ribbon, a novel BTB-domain containing nuclear protein, in the elongation of two epithelial tubes: the Drosophila salivary gland and trachea. We show that Ribbon interacts with Lola Like, another BTB-domain containing protein required for robust nuclear localization of Ribbon, to upregulate crumbs expression and downregulate Moesin activity. Our ultrastructural analysis of ribbon null salivary glands by TEM reveals a diminished pool of subapical vesicles and an increase in microvillar structure, cellular changes consistent with the known role of Crumbs in apical membrane generation and of Moesin in the cross-linking of the apical membrane to the subapical cytoskeleton. Furthermore, the subapical localization of Rab11, a small GTPase associated with apical membrane delivery and rearrangement, is significantly diminished in ribbon mutant salivary glands and tracheae. These findings suggest that Ribbon and Lola Like function as a novel transcriptional cassette coordinating molecular changes at the apical membrane of epithelial cells to facilitate tube elongation.