Giet:Research

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Third-instar Drosophila larval brain


During mitosis, the mitotic spindle, a microtubule-based structure, plays a crucial role to define the plane of cell division and to ensure the proper segregation of sister chromatids into the future daughter cells. Errors in spindle formation can lead to mitotic delay, but also to improper chromosome segregation and aneuploidy, a common hallmark of most cancers. Moreover, in polarised stem cells, mitotic spindle orientation failure along the apico-basal axis triggers missegregation of cortical cell fates and overproliferation. Thus, a better understanding of the regulation of the microtubule network regulation by Microtubule Associated proteins (MAPS) would therefore constitute an important advance in order to understand the relationships between mitotic spindle morphogenesis and cancer.

Brains subjected to 3 days of RNAi and stained for phospho-histone H3 (blue) tubulin (green) and PKC (red, as an apical marker). Left: Control neuroblast during metaphase. Right: a monopolar spindle induced after klp61F RNAi.
Our project is to identify key components of the fly (Drosophila melanogaster) microtubule interactome by combination of biochemistry and proteomics. We propose to analyse the contribution of new putative MAPs for mitotic spindle assembly and orientation along the polarity axis of stem cells, 2 key processes leading to tissue-controlled cell proliferation and homeostasis.




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