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Publication

Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells.

Developmental cell | 2019

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 regulating MSO 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.

Pubmed ID: 31130353 RIS Download

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Associated grants

Agency: NCI NIH HHS, United States
Id: P30 CA023074
Agency: NIGMS NIH HHS, United States
Id: R01 GM110166
Agency: NIGMS NIH HHS, United States
Id: R01 GM126035
Agency: NIGMS NIH HHS, United States
Id: R35 GM136265

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