Developing novel tools to characterize Notch-triggered malignancy in the central nervous system of Drosophila melanogaster
Αναγνωστόπουλος, Γεράσιμος Γ.
During larval neurogenesis of the fruitfly Drosophila melanogaster, Notch signaling contributes to cell-fate decisions in the neuroblast lineage (Artavanis-Tsakonas et al., 1995; Kopan and Ilagan, 2009). However, in case of Notch aberrant activity, a hyperplastic central nervous system of neoplastic transition capacity may arise (Zacharioudaki et al., 2012; Zacharioudaki et al., 2016; Magadi et al., in preparation). We focus on the contribution of Notch signaling in generating malignant tumor phenotype. To address the neoplastic transition, we have utilized the “tissue allograft” method (Gateff, 1994; Rossi and Gonzalez, 2015) in order to transplant Notch-derived and HES-derived hyperplastic brain lobes into healthy hosts. In the future, we plan to perform transcriptome analysis of the Notch-triggered outgrown tumor including its temporal dynamics. We also aim to estimate the extent (if any) upon which Notch-derived tumors provoke tumor cell infiltration within healthy tissues and metastases development.
Finally, we have developed a novel genetic scheme in order to address whether the Notch hyperactivity that initiates the tumor outgrowth is still necessary to sustain tumor propagation. To address this hypothesis, we have generated a new transgenic D. melanogaster line carrying the UAS-FRT-NotchΔΕ-p2A-DsRed-FRT-nlsEGFP (U-NPDG) transgene. When crossed to a neuroblast-lineage-specific Gal4-expressing line, U-NPDG transgenic flies have been shown to induce central nervous system hyperplasia during larval neurogenesis.