Deltex modulates Dpp morphogen gradient formation and affects Dpp signaling in Drosophila.

Deltex (Dx) is a context-dependent regulator of Notch signaling that can act in a non-canonical fashion by facilitating the endocytosis of the Notch receptor. In an RNAi-based modifier screen of kinases and phosphatases, we identified Thickveins (Tkv), the receptor of Decapentaplegic (Dpp), as one of the interactors of Dx. Dpp, a Drosophila homolog of TGF-ß and bone morphogenetic proteins, acts as a morphogen to specify cell fate along the anterior-posterior axis of the wing. Tight regulation of Dpp signaling is thus indispensable for its proper functioning. Here, we present Dx as a novel modulator of Dpp signaling. We show evidence for the very first time that dx genetically interacts with dpp and its pathway components. Immunocytochemical analysis revealed that Dx colocalizes with Dpp and its receptor Tkv in Drosophila third-instar larval tissues. Furthermore, Dx was also seen to modulate the expression of dpp and its target genes, and we attribute this modulation to the involvement of Dx in the endocytosis and trafficking of Dpp. This study thus presents a whole new avenue of Dpp signaling regulation via the cytoplasmic protein Dx. This article has an associated First Person interview with the first author of the paper.

E3 ubiquitin ligase Deltex facilitates the expansion of Wingless gradient and antagonizes Wingless signaling through a conserved mechanism of transcriptional effector Armadillo/ß-catenin degradation.

The Wnt/Wg pathway controls myriads of biological phenomena throughout the development and adult life of all organisms across the phyla. Thus, an aberrant Wnt signaling is associated with a wide range of pathologies in humans. Tight regulation of Wnt/Wg signaling is required to maintain proper cellular homeostasis. Here, we report a novel role of E3 ubiquitin ligase Deltex in Wg signaling regulation. Drosophila dx genetically interacts with wg and its pathway components. Furthermore, Dx LOF results in a reduced spreading of Wg while its over-expression expands the diffusion gradient of the morphogen. We attribute this change in Wg gradient to the endocytosis of Wg through Dx which directly affects the short- and long-range Wg targets. We also demonstrate the role of Dx in regulating Wg effector Armadillo where Dx down-regulates Arm through proteasomal degradation. We also showed the conservation of Dx function in the mammalian system where DTX1 is shown to bind with ß-catenin and facilitates its proteolytic degradation, spotlighting a novel step that potentially modulates Wnt/Wg signaling cascade.