Lucie Vaufrey

Study of the role of Aurora-A kinase in the development of the larva and the brain of Drosophila melanogaster

Abstract :

Aurora-A (AurA) is a major kinase playing various roles in cell cycle. It’s a well- known oncogene and companies are developing drugs inhibiting its kinase activity. However, it has been shown in different species that AurA can have a kinase independent role or act as a tumor suppressor when its kinase activity is altered. This represents a problem for drugs development as inhibiting AurA kinase activity only could lead to life threatening phenotypes. To address this dilemma, we carefully deciphered phenotypes of AurA null and AurA hypomorph mutants in Drosophila, melanogaster using the pupation as readout for development timing and larval central brain neuroblasts as model for tumorigenic study. One readout to define a tumor suppressor in this model is a brain overgrowth phenotype associated to central brain neuroblasts over-proliferation. In AurA mutants, brain size appears slightly smaller until 96h of larval development. However, pupation occurring normally between 96 and 120h of larval development is delayed in AurA mutants and larvae have an increased size. In this “delayed” mutant larvae, brains are eventually bigger than wild-type controls. Furthermore, AurA mutant central brains show a huge increased number of cells positive for deadpan, a marker of neuroblast identity, even before the appearance of brain over-growth phenotype. Additionally, wing discs and ring glands are clearly smaller in AurA mutants at 96h compared to control and mutant larvae reach L2 and L3 developmental stage earlier than control. In conclusion, AurA mutants have: 1) a precocious developmental advance certainly related to ring gland growth defect; 2) a pupation delay which resembles Ecdysone pathway timing defects certainly due to wing discs growth defect; 3) an enlarged brains phenotype due to an increased of the number of neuroblast-like cells and the pupation delay.

Financial support :
Ligue Nationale Contre le Cancer & Région Bretagne

Committee : : October 2nd 2017
Claude PRIGENT (PhD co-director)
Stéphanie LE BRAS (PhD co-director)




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