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Calibrated mitotic oscillator drives motile ciliogenesis

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Science  05 Oct 2017:
eaan8311
DOI: 10.1126/science.aan8311

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Abstract

Cell division and differentiation depend on massive and rapid organelle remodeling. The mitotic oscillator, centered on the Cdk1-APC/C axis, spatiotemporally coordinates this reorganization in dividing cells. Here, we discovered that non-dividing cells could also implement this mitotic clock-like regulatory circuit to orchestrate subcellular reorganization associated with differentiation. We probed centriole amplification in differentiating mouse brain multiciliated cells. These post-mitotic 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 post-mitotic progenitors into mitosis. Thus, post-mitotic cells can redeploy and calibrate the mitotic oscillator to uncouple cytoplasmic from nuclear dynamics for organelle remodeling associated with differentiation.

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