Egfr/Ras signaling regulates DE-cadherin/Shotgun localization to control vein morphogenesis in the Drosophila wing

Abstract

Egfr/Ras signaling promotes vein cell fate specification in the developing Drosophila wing. While the importance of Ras signaling in vein determination has been extensively documented, the mechanisms linking Ras activity to vein differentiation remain unclear. We found that Ras signaling regulates both the levels and subcellular localization of the cell adhesion molecule DE-cadherin/Shotgun (Shg) in the differentiating wing epithelium. High Ras activity in presumptive vein cells directs the apical localization of Shg containing adherens junctions, whereas low Ras activity in intervein cells allows Shg to relocalize basally. These alterations in Shg-mediated adhesion control cell shape changes that are essential for vein morphogenesis. While Decapentaplegic (Dpp) acts downstream of Ras to maintain vein cell identity in the pupal wing, our results indicate that Ras controls Shg localization via a Dpp-independent mechanism. Ras, therefore, regulates both the transcriptional responses necessary for vein cell identity, and the cell adhesive changes that determine vein and intervein cell morphology.

Identification of Novel Ras-Cooperating Oncogenes in Drosophila melanogaster: A RhoGEF/Rho-Family/JNK Pathway Is a Central Driver of Tumorigenesis

“…Thus, Ras ACT does not cooperate by simply blocking cell death, although it is possible that its cell survival function could contribute to the cooperative effects. Therefore, Ras ACT must be providing other functions, such as promoting cell growth and proliferation or affecting cell-cell adhesion, as has been previously reported (Prober and Edgar 2000;Prober and Edgar 2002;O'keefe et al 2007), and we have observed in cooperative tumorigenesis with scrib mutants (Brumby and Richardson 2003).…”

An O-Glycosyltransferase Promotes Cell Adhesion during Development by Influencing Secretion of an Extracellular Matrix Integrin Ligand

“…Very specific localization of both was observed at the basal cell layer interface during two separate stages of adhesion (6 -8 h after puparium formation (APF) and 34 -42 h APF) (Fig. 2, A and AЈ and D-EЈ), similar to what was previously seen for integrins (40,46). Localization of both O-glycans and Tiggrin was diffuse during stages of separation of the epithelial cell layers (18 -20 h APF) (Fig.…”

“…Samples were then incubated with primary antibody overnight at 4°C in blocking buffer. Primary antibodies used were mouse anti-␤-PS-integrin (40) were used. Nuclei were stained with 4Ј,6-diamidino-2-phenylindole, dihydrochloride (DAPI) (Sigma, 1:1000).…”

Drosophila: A Model System That Allows in vivo Manipulation and Study of Epithelial Cell Polarity

“…The down-regulation of E-Cad by Src promotes EMT because it alters E-Cad trafficking by redirecting E-Cad from a recycling pathway to a lysosomal pathway (Shen et al, 2008). In both mammalian and Drosophila cells, EGF signaling also induces the MAPK (mitogen-activated protein kinase) pathway which leads to E-Cad and claudin expression and subsequent translocation of junctional proteins from the cytoplasm to cell-cell contacts (O'Keefe et al, 2007;Wang et al, 2006). E-Cad and EGF receptor interact at cell-cell contacts to negatively regulate the MAPK pathway in mammalian cells, suggesting a general negative feedback loop to regulate adhesion and junctional integrity (Qian et al, 2004).…”