<i>Cyclin O</i>
            (
            <i>Ccno</i>
            ) functions during deuterosome‐mediated centriole amplification of multiciliated cells

Funk, Maja C; Bera, Agata; Menchen, Tabea; Kuales, Georg; Thriene, Kerstin; Lienkamp, Soeren S.; Dengjel, Jörn; Omran, Heymut; Frank, Marcus; Arnold, Sebastian J.

doi:10.15252/embj.201490805

Cited by 78 publications

(122 citation statements)

References 30 publications

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“…Although CCNO partners and function are unknown, patients with mutations in ccno have MCCs with reduced number of cilia ). In particular, ccno mutant mice tracheal cells display larger deuterosomes with fewer proBBs suggesting a role for CCNO in the early onset of amplification (Funk et al 2015).…”

Section: Molecular Controlmentioning

confidence: 99%

“…1) (Stubbs et al 2012;Ma et al 2014;Wallmeier et al 2014), a cyclin-like protein first shown to be involved in oocyte meiosis resumption and apoptosis (Roig et al 2009;Ma et al 2013), and then shown to be expressed in MCC progenitors in the Xenopus skin and in the mouse brain, airways, and oviducts (Stubbs et al 2012;Funk et al 2015;Amirav et al 2016). Although its partners and molecular function remain to be determined, CCNO mutations or depletion lead to defects comparable to the C-MYB phenotype: defects in BB amplification, docking, and ciliogenesis Funk et al 2015). In humans, mutations in CCNO have been identified as a cause of RGMC and associated with hydrocephalus and female infertility Amirav et al 2016).…”

Section: Downstream Effectors Of the MCC Differentiation Programmentioning

confidence: 99%

“…Under the control of MCIDAS/E2F complex and involving C-MYB transcription factor, the expression levels of CEP63, CEP152, and PLK4, among others, is increased at the onset of differentiation (Hoh et al 2012;Klos Dehring et al 2013;Wang et al 2013;Zhao et al 2013;Ma et al 2014;Funk et al 2015). In addition, a paralog of CEP63, CCDC67 (also called deuterosome protein 1, DEUP1) is specifically expressed in vertebrate multiciliated tissues (Zhao et al 2013;Ma et al 2014).…”

Section: Molecular Controlmentioning

confidence: 99%

“…2). Although the BB duplication players downstream from SAS-6 are also up-regulated during vertebrate MCC differentiation, their involvement in centriole amplification remains to be determined (Hoh et al 2012;Klos Dehring et al 2013;Wang et al 2013;Zhao et al 2013;Ma et al 2014;Funk et al 2015).…”

Section: Molecular Controlmentioning

confidence: 99%

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Multiciliated Cells in Animals

Meunier¹,

Azimzadeh²

2016

Cold Spring Harb Perspect Biol

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Many animal cells assemble single cilia involved in motile and/or sensory functions. In contrast, multiciliated cells (MCCs) assemble up to 300 motile cilia that beat in a coordinate fashion to generate a directional fluid flow. In the human airways, the brain, and the oviduct, MCCs allow mucus clearance, cerebrospinal fluid circulation, and egg transportation, respectively. Impairment of MCC function leads to chronic respiratory infections and increased risks of hydrocephalus and female infertility. MCC differentiation during development or repair involves the activation of a regulatory cascade triggered by the inhibition of Notch activity in MCC progenitors. The downstream events include the simultaneous assembly of a large number of basal bodies (BBs)-from which cilia are nucleated-in the cytoplasm of the differentiating MCCs, their migration and docking at the plasma membrane associated to an important remodeling of the actin cytoskeleton, and the assembly and polarization of motile cilia. The direction of ciliary beating is coordinated both within cells and at the tissue level by a combination of planar polarity cues affecting BB position and hydrodynamic forces that are both generated and sensed by the cilia. Herein, we review the mechanisms controlling the specification and differentiation of MCCs and BB assembly and organization at the apical surface, as well as ciliary assembly and coordination in MCCs.

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Section: Molecular Controlmentioning

confidence: 99%

Section: Downstream Effectors Of the MCC Differentiation Programmentioning

confidence: 99%

Section: Molecular Controlmentioning

confidence: 99%

Section: Molecular Controlmentioning

confidence: 99%

See 2 more Smart Citations

Multiciliated Cells in Animals

Meunier¹,

Azimzadeh²

2016

Cold Spring Harb Perspect Biol

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“…Thus, Foxn4 needs to be re-examined in mouse MCCs, especially as partial genetic redundancy in the pathways that drive MCC differentiation has become a recurring theme. For example, mutations in two crucial regulators of MCC differentiation, namely Ccno and Myb, cause severe defects in MCC differentiation in the mouse lung initially but also eventually recover, at least superficially, over time (Funk et al, 2015;Tan et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Foxn4 promotes gene expression required for the formation of multiple motile cilia

2016

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Multiciliated cell (MCC) differentiation involves extensive organelle biogenesis required to extend hundreds of motile cilia. Key transcriptional regulators known to drive the gene expression required for this organelle biogenesis are activated by the related coiled-coil proteins Multicilin and Gemc1. Here we identify foxn4 as a new downstream target of Multicilin required for MCC differentiation in Xenopus skin. When Foxn4 activity is inhibited in Xenopus embryos, MCCs show transient ciliogenesis defects similar to those seen in mutants of Foxj1, a known key regulator of genes required for motile ciliation. RNAseq analysis indicates that Foxn4 co-activates some Foxj1 target genes strongly and many Foxj1 targets weakly. ChIPseq suggests that whereas Foxn4 and Foxj1 frequently bind to different targets at distal enhancers, they largely bind together at MCC gene promoters. Consistent with this co-regulation, cilia extension by MCCs is more severely compromised in foxn4 and foxj1 double mutants than in single mutants. In contrast to Foxj1, Foxn4 is not required to extend a single motile cilium by cells involved in left-right patterning. These results indicate that Foxn4 complements Foxj1 transcriptionally during MCC differentiation, thereby shaping the levels of gene expression required for the timely and complete biogenesis of multiple motile cilia.

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The MIR34B/C genomic region contains multiple potential regulators of multiciliogenesis

et al. 2023

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The MIR449 genomic locus encompasses several regulators of multiciliated cell (MCC) formation (multiciliogenesis). The miR-449 homologs miR-34b/c represent additional regulators of multiciliogenesis that are transcribed from another locus. Here, we characterized the expression of BTG4, LAYN, and HOATZ, located in the MIR34B/C locus using single-cell RNA-seq and super-resolution microscopy from human, mouse, or pig multiciliogenesis models. BTG4, LAYN, and HOATZ transcripts were expressed in both precursors and mature MCCs. The Layilin/LAYN protein was absent from primary cilia, but it was expressed in apical membrane regions or throughout motile cilia. LAYN silencing altered apical actin cap formation and multiciliogenesis. HOATZ protein was detected in primary cilia or throughout motile cilia. Altogether, our data suggest that the MIR34B/C locus may gather potential actors of multiciliogenesis.

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Cyclin O ( Ccno ) functions during deuterosome‐mediated centriole amplification of multiciliated cells

Cited by 78 publications

References 30 publications

Multiciliated Cells in Animals

Multiciliated Cells in Animals

Foxn4 promotes gene expression required for the formation of multiple motile cilia

The MIR34B/C genomic region contains multiple potential regulators of multiciliogenesis

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