Glioblastoma Models in Drosophila melanogaster

Abstract

Glioblastoma (GB) is the most common and malignant brain tumour with a median survival of 15 months. The genetic basis of GB is heterogeneous, but mutations in EGFR and PI3K pathways are the most frequent. The need of novel models to decipher molecular mechanisms underlying GB progression has brought Drosophila melanogaster as an optimal candidate. The power of fly genetics, the development of novel gene expression and visualisation techniques and genetic and drug screenings put Drosophila in an advantageous position. Moreover, the evolutionary conserved function of glial cells allows an extrapolation of the results towards a clinical view.

Key Concepts

  • Glial functions are evolutionary conserved along animal kingdom.
  • Drosophila is a suitable model to study gene networks in GB.
  • The wide collection of experimental tools in Drosophila facilitates the modulation and detection of signalling pathways.
  • Drosophila is a valid model to validate therapeutical platforms.
  • Glioblastoma to neuron communication plays a central role in tumor progression and neurodegeneration.

Keywords: glioblastoma; Drosophila; PI3K; EGFR; model organism; tumour microtubes; RIO kinases; vesicle transport; wingless

Figure 1. Electron microscopy images of Drosophila brain samples. Neurons are coloured in blue, and glia/glioma cells are coloured in magenta. Glial membranes intercalate within neuronal tissue in healthy brains (a). Glial membranes in glioma samples expand, change morphology and infiltrate throughout healthy tissue (b).
Figure 2. Drosophila glia in the adult brain. (a) Adult brain where the areas occupied by the different glial types are colour coded. (b) Details of position of different glial types.
Figure 3. Schematic representation of glioblastoma and neuron communication. GB cells project tumour microtubes (TMs) that accumulate Fz1 receptor (red triangle). TMs enwrap and vampirise Wg (green balls) from healthy neurons, as a consequence neurons degenerate (synapse loss) and GB cells increase Wg signalling that stimulates proliferation.
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Losada‐Pérez, María, Jarabo, Patricia, Martín‐Castro, Francisco A, and Casas‐Tintó, Sergio(May 2020) Glioblastoma Models in Drosophila melanogaster. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022540.pub2]