Abstract
SummaryThe cilia and cell cycles are inextricably linked. Centrioles in the basal body of cilia nucleate the ciliary axoneme and sequester pericentriolar matrix (PCM) at the centrosome to organize the mitotic spindle. Cilia themselves respond to growth signals, prompting cilia resorption and cell cycle re-entry. We describe a fluorescent cilia and cell cycle biosensor allowing live imaging of cell cycle progression and cilia assembly and disassembly kinetics in cells and inducible mice. We define assembly and disassembly in relation to cell cycle stage with single-cell resolution and explore the intercellular heterogeneity in cilia kinetics. In all cells and tissues analyzed, we observed cilia that persist through the G1/S transition and into S/G2/M-phase. We conclude that persistence of cilia after the G1/S transition is a general property. This resource will shed light at an individual cell level on the interplay between the cilia and cell cycles in development, regeneration, and disease.
Highlights
Cilia are microtubule-based cellular projections that come in motile and non-motile forms. They sense key mechanical and environmental cues including the transduction of mitogenic signals that include Hedgehog (HH), insulin-like growth factor 1 (IGF-1), and platelet-derived growth factor (PDGF) (Goetz and Anderson, 2010)
Primary cilia are dynamic organelles whose assembly and resorption are inextricably coupled with cell cycle progression
Evidence exists for extensive molecular crosstalk between ciliary factors and key cell cycle regulators; for example, the anaphase promoting complex (APC) may be sequestered at the cilium and localized cell cycle-dependent proteolysis of the CDK5-SCF-Nde1 axis may trigger cell cycle progression (Maskey et al, 2015; Pugacheva et al, 2007; Wang et al, 2014)
Summary
Cilia are microtubule-based cellular projections that come in motile and non-motile forms. They sense key mechanical and environmental cues including the transduction of mitogenic signals that include Hedgehog (HH), insulin-like growth factor 1 (IGF-1), and platelet-derived growth factor (PDGF) (Goetz and Anderson, 2010). The structural and functional diversity of mammalian cilia likely underlies the huge spectrum of phenotypes observed in ciliopathy patients (Reiter and Leroux, 2017). Primary cilia are dynamic organelles whose assembly and resorption are inextricably coupled with cell cycle progression. The spatially distinct dual functions of the centrioles as structural components of both the basal body of the cilium and centrosomes at the poles of the mitotic spindle likely contribute to this coordination. Evidence exists for extensive molecular crosstalk between ciliary factors and key cell cycle regulators; for example, the anaphase promoting complex (APC) may be sequestered at the cilium and localized cell cycle-dependent proteolysis of the CDK5-SCF-Nde axis may trigger cell cycle progression (Maskey et al, 2015; Pugacheva et al, 2007; Wang et al, 2014)
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