期刊
DEVELOPMENTAL CELL
卷 50, 期 1, 页码 11-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2019.04.036
关键词
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资金
- ERC starting grant CentroStemCancer [242598]
- Institut Curie
- CNRS
- NCI [P30CA23074]
- NIGMS [R01 GM110166, GM126035]
- FRM
- IC
- FRM installation grant
- ATIP grant
- European Research Council (ERC) [242598] Funding Source: European Research Council (ERC)
Defects in mitotic spindle orientation (MSO) disrupt the organization of stem cell niches impacting tissue morphogenesis and homeostasis. Mutations in centrosome genes reduce MSO fidelity, leading to tissue dysplasia and causing several diseases such as microcephaly, dwarfism, and cancer. Whether these mutations perturb spindle orientation solely by affecting astral microtubule nucleation or whether centrosome proteins have more direct functions in regulatingMSO is unknown. To investigate this question, we analyzed the consequences of deregulating Plk4 (the master centriole duplication kinase) activity in Drosophila asymmetrically dividing neural stem cells. We found that Plk4 functions upstream of MSO control, orchestrating centriole symmetry breaking and consequently centrosome positioning. Mechanistically, we show that Plk4 acts through Spd2 phosphorylation, which induces centriole release from the apical cortex. Overall, this work not only reveals a role for Plk4 in regulating centrosome function but also links the centrosome biogenesis machinery with the MSO apparatus.
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