Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells

Abstract

How cells count and regulate organelle number is a fundamental question in cell biology. For example, most cells restrict centrioles to two in number and assemble one cilium; however, multiciliated cells (MCCs) synthesize hundreds of centrioles to assemble multiple cilia. Aberration in centriole/cilia number impairs MCC function and can lead to pathological outcomes. Yet how MCCs control centriole number remains unknown. Using Xenopus, we demonstrate that centriole number scales with apical area over a remarkable 40-fold change in size. We find that tensile forces that shape the apical area also trigger centriole amplification based on both cell stretching experiments and disruption of embryonic elongation. Unexpectedly, Piezo1, a mechanosensitive ion channel, localizes near each centriole suggesting a potential role in centriole amplification. Indeed, depletion of Piezo1 affects centriole amplification and disrupts its correlation with the apical area in a tension dependent manner. Thus, mechanical forces calibrate cilia/centriole number to the MCC apical area via Piezo1. Our results provide new perspectives to study organelle number control essential for optimal cell function.

Local synchronization of cilia and tissue-scale cilia alignment are sufficient for global metachronal waves

“…From the abovementioned values, we calculated the distance between cilia to be 0.68 μm, and a cellular density of 2.74 cilia/μm 2 . Altogether, our results revealed that multiciliated cells in the four-day old zebrafish nose contain fewer cilia than multiciliated cells of the lung epithelium (>100 cilia per cell) 47 or Xenopus laevis embryonic skin (∼150 cilia per cell) 48, 49 , but retain a similar cilia density due to their reduced apical surface (Fig. 1E).…”

“…(E) A graph depicting ciliary density per cell across animals and organs. Shown are the zebrafish nose, clawed frog skin (47,48), mouse brain ventricles (49), lungs (46), and oviduct (50). All n refer to the number of fish.…”

Male infertility‐associated Ccdc108 regulates multiciliogenesis via the intraflagellar transport machinery

“…Since both Ccdc108 and Ift74 function upstream of axoneme formation in centriole migration/docking to the apical surface, which starts from earlier developmental stages (Kulkarni et al , 2021), we set out to investigate the distributions of Ccdc108 and IFT‐B complex proteins in MCCs of embryos at stage 18. Interestingly, both Ccdc108 and IFT‐B complex proteins displayed centriolar localization when centriole migration to the apical surface is expected to be occurring at this stage (Fig 7A and B), supporting involvement of Ccdc108 and IFT‐B proteins in regulating early steps of multiciliation before axoneme elongation.…”

PLK4 drives centriole amplification and apical surface area expansion in multiciliated cells

“…Centriole number scales with apical surface area in multiciliated mTECs and Xenopus embryonic epidermis (Nanjundappa et al 2019; Kulkarni et al 2021). In Xenopus , mechanical stretching forces help couple centriole number with MCC apical area (Kulkarni et al 2021). However, while mouse MCCs amplify centrioles in a single round of centriole biogenesis, Xenopus epidermal MCCs cells produce centrioles in two distinct waves (Al Jord et al 2014; Kulkarni et al 2021).…”