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Identifier 000443443
Title Haemocyte and tumor interplay in a neural stem-cell-derived model of tumorigenesis in Drosophila melanogaster
Alternative Title Αλληλεπίδραση αιμοκυττάρων και νευροβλαστικών καρκινικών κυττάρων στη μύγα
Author Βλαχόπουλος, Νικόλαος Δ.
Thesis advisor Δελιδάκης, Χρήστος
Reviewer Παυλόπουλος, Αναστάσιος
Μπέρτσιας, Γεώργιος
Abstract Drosophila melanogaster is an ideal system to study stem cell biology and innate immune responses. Through its genetic tractability and the evolutionary conservation of molecular effectors, the fly constitutes a workhorse for functional and lineage tracing studies. In this work, we built upon recent advances in innate immunity concerning tumorigenesis by incorporating a model of allograft series from neural-derived (primary) tumors. Powerful genetic tools allowed us to, temporally, obscure the lineage progression of the neural stem cell population (neuroblasts), specifically, in the larval brain. During larval neurogenesis, the majority of the adult neurons and glia are generated from asymmetric divisions of these neural stem-like cells. Neuroblasts (NBs) are endowed with spatiotemporal cues that unfold a highly stereotyped and dynamic transcriptional trajectory during the asymmetric segregation of their daughter cells, called ganglion mother cells (GMCs). This remarkable division mode ensures two distinct fates. First, NBs retain their stemlike characteristics, performing repeated rounds of asymmetric division. Second, the resultant GMCs are gradually specified and divide once more to generate post-mitotic neurons/glia. Notchsignaling and a plethora of conserved effectors are essential for the developmental orchestration of proper NB-lineage progression. Through RNA-interference (RNAi) we abrogated the self-renewal capacity of NBs by knocking-down the RNA-binding protein Imp (insulin-like growth factor II mRNA-binding protein) and the proto-oncogene Myc. In combination, we overactivated Nsignaling within the NB lineages during larval neurogenesis. This resulted to a hyperplastic larval central nervous system that facilitated the foothold for our experimental method. By injecting these primary tumors in adult hosts, we set out to explore the tumor progression in vivo. Previous work in our laboratory from Eva Zacharioudaki and Chrysanthi Voutiraki has shown close interaction between tumor secondary masses and the cellular arm of the fly’s immunity, called haemocytes. Part and parcel of the adult immunosurveillance system, haemocytes (plasmatocytes) exhibit phagocytic activity and active migratory behavior, mimicking the macrophage population of vertebrates. Focused on the neural stem cell-derived tumors and haemocyte interplay, we generated a survival screen of adult hosts deficient in haemocyte-specific genes (RNAi) and identified two scavenger-receptors as essential for preserving host lifespan during tumor progression. This work establishes an early view of the dynamics of tumor and haemocyte interaction and provides the framework of an in vivo model to decipher the fundamental mechanisms of tumorigenesis within an invertebrate system.
Language English
Issue date 2021-11-26
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work--Post-graduate theses
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