Journal
SCIENCE
Volume 358, Issue 6364, Pages 803-806Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aan8311
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Funding
- Region Ile-de-France [NERF 2011-45]
- Fondation pour la Recherche Medicale (FRM) [DGE 20111123023]
- Federation pour la Recherche sur le Cerveau-Rotary International France
- Agence Nationale de la Recherche (ANR) Investissements d'Avenir [ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSL* Research University]
- UPMC
- INSERM
- GEFLUC
- CNRS
- l'Ecole Normale Superieure (ENS)
- ANR [ANR-12-BSV4-0006, ANRJC JC-15-CE13-0005-01]
- European Research Council (ERC) [647466]
- FRM [FRM20140329547, FDT20150531994]
- Canceropole Ile-de-France [2014-1-PL BIO-11-INSERM 12-1]
- Fondation Pierre-Gilles de Gennes [FPGG03]
- Association pour la Recherche sur le Cancer [ARC PJA-20131200184]
- French Ministry of Higher Education and Research
- Labex MEMOLIFE
- Agence Nationale de la Recherche (ANR) [ANR-12-BSV4-0006] Funding Source: Agence Nationale de la Recherche (ANR)
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Cell division and differentiation depend on massive and rapid organelle remodeling. The mitotic oscillator, centered on the cyclin-dependent kinase 1-anaphase-promoting complex/cyclosome (CDK1-APC/C) axis, spatiotemporally coordinates this reorganization in dividing cells. Here we discovered that nondividing cells could also implement this mitotic clocklike regulatory circuit to orchestrate subcellular reorganization associated with differentiation. We probed centriole amplification in differentiating mouse-brain multiciliated cells. These postmitotic progenitors fine-tuned mitotic oscillator activity to drive the orderly progression of centriole production, maturation, and motile ciliation while avoiding the mitosis commitment threshold. Insufficient CDK1 activity hindered differentiation, whereas excessive activity accelerated differentiation yet drove postmitotic progenitors into mitosis. Thus, postmitotic cells can redeploy and calibrate the mitotic oscillator to uncouple cytoplasmic from nuclear dynamics for organelle remodeling associated with differentiation.
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