Centrosomes are cytoplasmic organelles found in most animal cells with important roles in polarity establishment and maintenance. Theodor Boveri s pioneering work first suggested that extra-centrosomes could contribute to genetic instability and consequently to tumourigenesis. Although many human tumours do exhibit centrosome amplification (extra centrosomes) or centrosome abnormalities, the exact contribution of centrosomes to tumour initiation in vertebrate organisms remains to be determined. I have recently showed that Drosophila flies carrying extra-centrosomes, following the over-expression of the centriole replication kinase Sak, did not exhibit chromosome segregation errors and were able to maintain a stable diploid genome over many generations. Surprisingly, however, neural stem cells fail frequently to align the mitotic spindle with their polarity axis during asymmetric division. Moreover, I have found that centrosome amplification is permissive to tumour formation in flies. So far, however, we do not know the molecular mechanisms that allow transformation when extra centrosomes are present and elucidating these mechanisms is the aim of the work presented in this proposal. Here, I describe a series of complementary approaches that will help us to decipher the link between centrosomes, stem cells and tumour biology. In addition, I wish to pursue the original observations made in Drosophila and investigate the consequences of centrosome amplification in mammals.
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