Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells

Davide Gambarotto, Carole Pennetier, John M. Ryniawec, Daniel W. Buster, Delphine Gogendeau, Alix Goupil, Maddalena Nano, Anthony Simon, Damien Blanc, Victor Racine, Yuu Kimata, Gregory C. Rogers, Renata Basto

Research output: Contribution to journalArticle

Abstract

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. Mitotic spindle orientation is tightly regulated during development and adulthood to maintain tissue organization and homeostasis. Spindle orientation requires the coordination between centrosomes and cortical cues. Gambarotto et al. report that the centrosome components Plk4 and Spd2 regulate centrosome asymmetry in interphase to influence spindle positioning in mitosis.

Original languageEnglish (US)
Pages (from-to)11-24.e10
JournalDevelopmental Cell
Volume50
Issue number1
DOIs
StatePublished - Jul 1 2019

Fingerprint

Centrioles
Centrosome
Neural Stem Cells
Stem cells
Spindle Apparatus
Tissue
Phosphorylation
Machinery
Nucleation
Phosphotransferases
Genes
Defects
Homeostasis
Stem Cell Niche
Dwarfism
Microcephaly
Mutation
Interphase
Proteins
Morphogenesis

Keywords

  • centrosome positioning
  • centrosomes
  • Plk4
  • Spd2
  • spindle orientation
  • symmetry breaking

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Gambarotto, D., Pennetier, C., Ryniawec, J. M., Buster, D. W., Gogendeau, D., Goupil, A., ... Basto, R. (2019). Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells. Developmental Cell, 50(1), 11-24.e10. https://doi.org/10.1016/j.devcel.2019.04.036

Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells. / Gambarotto, Davide; Pennetier, Carole; Ryniawec, John M.; Buster, Daniel W.; Gogendeau, Delphine; Goupil, Alix; Nano, Maddalena; Simon, Anthony; Blanc, Damien; Racine, Victor; Kimata, Yuu; Rogers, Gregory C.; Basto, Renata.

In: Developmental Cell, Vol. 50, No. 1, 01.07.2019, p. 11-24.e10.

Research output: Contribution to journalArticle

Gambarotto, D, Pennetier, C, Ryniawec, JM, Buster, DW, Gogendeau, D, Goupil, A, Nano, M, Simon, A, Blanc, D, Racine, V, Kimata, Y, Rogers, GC & Basto, R 2019, 'Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells', Developmental Cell, vol. 50, no. 1, pp. 11-24.e10. https://doi.org/10.1016/j.devcel.2019.04.036
Gambarotto D, Pennetier C, Ryniawec JM, Buster DW, Gogendeau D, Goupil A et al. Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells. Developmental Cell. 2019 Jul 1;50(1):11-24.e10. https://doi.org/10.1016/j.devcel.2019.04.036
Gambarotto, Davide ; Pennetier, Carole ; Ryniawec, John M. ; Buster, Daniel W. ; Gogendeau, Delphine ; Goupil, Alix ; Nano, Maddalena ; Simon, Anthony ; Blanc, Damien ; Racine, Victor ; Kimata, Yuu ; Rogers, Gregory C. ; Basto, Renata. / Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells. In: Developmental Cell. 2019 ; Vol. 50, No. 1. pp. 11-24.e10.
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