The cell cycle variant in multiciliated cells incorporates 2 centriole biogenesis cycles

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Abstract
Multiciliated cell (MCC) differentiation is a calibrated version of the canonical cell cycle. The MCC cell cycle variant sustains amplification of centrioles for the nucleation of dozens of motile cilia, while avoiding cell division. In this study, we show that the MCC cell cycle variant is an accelerated version of the canonical cell cycle, which superposes two cycles of centriole biogenesis, in order to obtain multiple mature centrioles within a single -instead of double- cell cycle iteration. We further show that the precocious maturation of amplified procentrioles is even determinant for their spatial self-organization, disengagement and apical migration for cilia nucleation. Our findings collectively suggest that the decomposition of centriole biogenesis over two cycle iterations in dividing cells may have been adopted to ensure the growth of a solitary primary cilium, and exemplify how minimal deviations of the canonical cell cycle allow MCC progenitors to both amplify, and accelerate, centriole biogenesis for vital motile ciliogenesis.
Funding Information
  • Agence Nationale de la Recherche (ANR-19-CE13-0027)
  • Agence Nationale de la Recherche (ANR-21-CE16-0016)
  • Fondation pour la Recherche Médicale (EQU202103012767)
  • MEC | Agencia Estatal de Investigación (PID2024-157329NA-I00)
  • Centro de Biología Molecular Severo Ochoa (CEX2020-001049-S)
  • Centro de Biología Molecular Severo Ochoa (MCIN/AEI /10.13039/501100011033)
  • Hartwell Foundation (R01GM133897)
  • Hartwell Foundation (R01GM114119)
  • Hartwell Foundation (R01CA266199)
  • Ligue Contre le Cancer (IP/SC-16052)
  • Damon Runyon Cancer Research Foundation (Merck Fellow DRG-2478-22)
  • EC | European Research Council (10.3030/647466)

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