Post-mitotic centriole disengagement and maturation leads to centrosome amplification in polyploid trophoblast giant cells.
Molecular biology of the cell
DNA replication is normally coupled with centriole duplication in the cell cycle. Trophoblast giant cells (TGCs) of the placenta undergo endocycles resulting in polyploidy but their centriole state is not known. We used a cell culture model for TGC differentiation to examine centriole and centrosome number and properties. Prior to differentiation, trophoblast stem cells (TSCs) have either two centrioles before duplication, or four centrioles after. We find that the average nuclear area increases approximately 8-fold over differentiation, but most TGCs do not have more than four centrioles. However, these centrioles become disengaged, acquire centrosome proteins, and can nucleate microtubules. In addition, some TGCs undergo further duplication and disengagement of centrioles, resulting in substantially higher numbers. Live imaging revealed that disengagement and separation are centriole autonomous and can occur asynchronously. Centriole amplification, when present, occurs by the standard mechanism of one centriole generating one procentriole. PLK4 inhibition blocks centriole formation in differentiating TGCs but does not affect endocycle progression. In summary, centrioles in TGC endocycles undergo disengagement and conversion to centrosomes. This increases centrosome number, but to a limited extent compared with DNA reduplication. [Media: see text] [Media: see text] [Media: see text] [Media: see text].
View details for DOI 10.1091/mbc.E22-05-0182
View details for PubMedID 36001376
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Cyclin-dependent kinase control of motile ciliogenesis
Cycling cells maintain centriole number at precisely two per cell in part by limiting their duplication to S phase under the control of the cell cycle machinery. In contrast, postmitotic multiciliated cells (MCCs) uncouple centriole assembly from cell cycle progression and produce hundreds of centrioles in the absence of DNA replication to serve as basal bodies for motile cilia. Although some cell cycle regulators have previously been implicated in motile ciliogenesis, how the cell cycle machinery is employed to amplify centrioles is unclear. We use transgenic mice and primary airway epithelial cell culture to show that Cdk2, the kinase responsible for the G1 to S phase transition, is also required in MCCs to initiate motile ciliogenesis. While Cdk2 is coupled with cyclins E and A2 during cell division, cyclin A1 is required during ciliogenesis, contributing to an alternative regulatory landscape that facilitates centriole amplification without DNA replication.
View details for PubMedID 30152757
Mitosis sans Mitosis: The Mitotic Oscillator in Differentiation
2017; 43 (4): 385–86
Differentiation and proliferation are usually considered to be antagonistic partners in development. However, in a recent issue of Science, Al Jord et al. (2017) show that key regulators of the mitotic cycle are redeployed in differentiating multiciliated cells to promote ciliogenesis without mitotic progression.
View details for PubMedID 29161589