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  1. Article ; Online: The cilia mechanosensation debate gets (bio)physical.

    Wachten, Dagmar / Mill, Pleasantine

    Nature reviews. Nephrology

    2023  Volume 19, Issue 5, Page(s) 279–280

    MeSH term(s) Humans ; Cilia ; Mechanotransduction, Cellular
    Language English
    Publishing date 2023-03-13
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2490366-8
    ISSN 1759-507X ; 1759-5061
    ISSN (online) 1759-507X
    ISSN 1759-5061
    DOI 10.1038/s41581-023-00701-4
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  2. Article ; Online: Primary cilia as dynamic and diverse signalling hubs in development and disease.

    Mill, Pleasantine / Christensen, Søren T / Pedersen, Lotte B

    Nature reviews. Genetics

    2023  Volume 24, Issue 7, Page(s) 421–441

    Abstract: Primary cilia, antenna-like sensory organelles protruding from the surface of most vertebrate cell types, are essential for regulating signalling pathways during development and adult homeostasis. Mutations in genes affecting cilia cause an overlapping ... ...

    Abstract Primary cilia, antenna-like sensory organelles protruding from the surface of most vertebrate cell types, are essential for regulating signalling pathways during development and adult homeostasis. Mutations in genes affecting cilia cause an overlapping spectrum of >30 human diseases and syndromes, the ciliopathies. Given the immense structural and functional diversity of the mammalian cilia repertoire, there is a growing disconnect between patient genotype and associated phenotypes, with variable severity and expressivity characteristic of the ciliopathies as a group. Recent technological developments are rapidly advancing our understanding of the complex mechanisms that control biogenesis and function of primary cilia across a range of cell types and are starting to tackle this diversity. Here, we examine the structural and functional diversity of primary cilia, their dynamic regulation in different cellular and developmental contexts and their disruption in disease.
    MeSH term(s) Adult ; Animals ; Humans ; Cilia/genetics ; Cilia/metabolism ; Signal Transduction ; Ciliopathies/genetics ; Ciliopathies/metabolism ; Mammals
    Language English
    Publishing date 2023-04-18
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2035157-4
    ISSN 1471-0064 ; 1471-0056
    ISSN (online) 1471-0064
    ISSN 1471-0056
    DOI 10.1038/s41576-023-00587-9
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  3. Article ; Online: Correction to: Live Imaging and Analysis of Cilia and Cell Cycle Dynamics with the Arl13bCerulean-Fucci2a Biosensor and Fucci Tools.

    Van Kerckvoorde, Melinda / Ford, Matthew J / Yeyati, Patricia L / Mill, Pleasantine / Mort, Richard L

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2329, Page(s) C3

    Language English
    Publishing date 2022-01-11
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1538-6_25
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  4. Article ; Online: Live Imaging and Analysis of Cilia and Cell Cycle Dynamics with the Arl13bCerulean-Fucci2a Biosensor and Fucci Tools.

    Van Kerckvoorde, Melinda / Ford, Matthew J / Yeyati, Patricia L / Mill, Pleasantine / Mort, Richard L

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2329, Page(s) 291–309

    Abstract: The cell and cilia cycles are inextricably linked through the dual functions of the centrioles at both the basal body of cilia and at mitotic centrosomes. How cilia assembly and disassembly, either through slow resorption or rapid deciliation, are ... ...

    Abstract The cell and cilia cycles are inextricably linked through the dual functions of the centrioles at both the basal body of cilia and at mitotic centrosomes. How cilia assembly and disassembly, either through slow resorption or rapid deciliation, are coordinated with cell cycle progression remains unclear in many cell types and developmental paradigms. Moreover, little is known about how additional cilia parameters including changes in ciliary length or frequency of distal tip shedding change with cell cycle stage. In order to explore these questions, we have developed the Arl13bCerulean-Fucci2a tricistronic cilia and cell cycle biosensor (Ford et al., Dev Cell 47:509-523.e7, 2018). This reporter allowed us to document the heterogeneity in ciliary behaviors during the cell cycle at a population level. Without the need for external stimuli, it revealed that in several cell types and in the developing embryo cilia persist beyond the G1/S checkpoint. Here, we describe the generation of stable cell lines expressing Arl13bCerulean-Fucci2a and open-source software to aid morphometric profiling of the primary cilium with cell cycle phases, including changes in cilium length. This resource will allow the investigation of multiple morphometric questions relating to cilia and cell cycle biology.
    MeSH term(s) 3T3 Cells ; Animals ; Biosensing Techniques/methods ; Cell Cycle ; Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/metabolism ; Cilia/metabolism ; Geminin/chemistry ; Geminin/metabolism ; Humans ; Luminescent Proteins/metabolism ; Mice ; Microscopy, Confocal ; Protein Domains ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/metabolism ; Red Fluorescent Protein
    Chemical Substances CDT1 protein, human ; Cell Cycle Proteins ; GMNN protein, human ; Geminin ; Luminescent Proteins ; Recombinant Fusion Proteins
    Language English
    Publishing date 2021-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1538-6_21
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  5. Article ; Online: A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease.

    Waddell, Scott H / Yao, Yuelin / Olaizola, Paula / Walker, Alexander / Jarman, Edward J / Gournopanos, Konstantinos / Gradinaru, Andreea / Christodoulou, Ersi / Gautier, Philippe / Boerrigter, Melissa M / Cadamuro, Massimiliano / Fabris, Luca / Drenth, Joost Ph / Kendall, Timothy J / Banales, Jesus M / Khamseh, Ava / Mill, Pleasantine / Boulter, Luke

    Science translational medicine

    2023  Volume 15, Issue 713, Page(s) eabq5930

    Abstract: The formation of multiple cysts in the liver occurs in a number of isolated monogenic diseases or multisystemic syndromes, during which bile ducts develop into fluid-filled biliary cysts. For patients with polycystic liver disease (PCLD), nonsurgical ... ...

    Abstract The formation of multiple cysts in the liver occurs in a number of isolated monogenic diseases or multisystemic syndromes, during which bile ducts develop into fluid-filled biliary cysts. For patients with polycystic liver disease (PCLD), nonsurgical treatments are limited, and managing life-long abdominal swelling, pain, and increasing risk of cyst rupture and infection is common. We demonstrate here that loss of the primary cilium on postnatal biliary epithelial cells (via the deletion of the cilia gene
    MeSH term(s) Humans ; Bile Ducts ; Cysts ; Extracellular Matrix ; Integrins
    Chemical Substances Integrins
    Language English
    Publishing date 2023-09-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abq5930
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    Zs.A 6941: Show issues Location:
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  6. Article: The effect of

    Horani, Amjad / Gupta, Deepesh Kumar / Xu, Jian / Xu, Huihui / Del Carmen Puga-Molina, Lis / Santi, Celia M / Ramagiri, Sruthi / Brennen, Steven K / Pan, Jiehong / Huang, Tao / Hyland, Rachael M / Gunsten, Sean P / Tzeng, Shin-Cheng / Strahle, Jennifer M / Mill, Pleasantine / Mahjoub, Moe R / Dutcher, Susan K / Brody, Steven L

    bioRxiv : the preprint server for biology

    2023  

    Abstract: DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 ... ...

    Abstract DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift null deletion in
    Brief summary: A mouse model of human DNAAF5 primary ciliary dyskinesia variants reveals gene dosage effects of mutant alleles and tissue-specific molecular requirements for cilia motor assembly.
    Language English
    Publishing date 2023-01-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.13.523966
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  7. Article ; Online: Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis.

    Hall, Emma A / Kumar, Dhivya / Prosser, Suzanna L / Yeyati, Patricia L / Herranz-Pérez, Vicente / García-Verdugo, Jose Manuel / Rose, Lorraine / McKie, Lisa / Dodd, Daniel O / Tennant, Peter A / Megaw, Roly / Murphy, Laura C / Ferreira, Marisa F / Grimes, Graeme / Williams, Lucy / Quidwai, Tooba / Pelletier, Laurence / Reiter, Jeremy F / Mill, Pleasantine

    eLife

    2023  Volume 12

    Abstract: Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by Pericentriolar material 1 (PCM1). To study the requirement for centriolar satellites, we generated mice lacking PCM1, a crucial component of satellites. ...

    Abstract Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by Pericentriolar material 1 (PCM1). To study the requirement for centriolar satellites, we generated mice lacking PCM1, a crucial component of satellites.
    MeSH term(s) Animals ; Female ; Humans ; Mice ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Centrioles/metabolism ; Centrosome/metabolism ; Cilia/metabolism ; Cytoskeletal Proteins/metabolism
    Chemical Substances Cell Cycle Proteins ; Cytoskeletal Proteins ; Pcm1 protein, mouse
    Language English
    Publishing date 2023-02-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.79299
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  8. Article ; Online: A WDR35-dependent coat protein complex transports ciliary membrane cargo vesicles to cilia.

    Quidwai, Tooba / Wang, Jiaolong / Hall, Emma A / Petriman, Narcis A / Leng, Weihua / Kiesel, Petra / Wells, Jonathan N / Murphy, Laura C / Keighren, Margaret A / Marsh, Joseph A / Lorentzen, Esben / Pigino, Gaia / Mill, Pleasantine

    eLife

    2021  Volume 10

    Abstract: Intraflagellar transport (IFT) is a highly conserved mechanism for motor-driven transport of cargo within cilia, but how this cargo is selectively transported to cilia is unclear. WDR35/IFT121 is a component of the IFT-A complex best known for its role ... ...

    Abstract Intraflagellar transport (IFT) is a highly conserved mechanism for motor-driven transport of cargo within cilia, but how this cargo is selectively transported to cilia is unclear. WDR35/IFT121 is a component of the IFT-A complex best known for its role in ciliary retrograde transport. In the absence of WDR35, small mutant cilia form but fail to enrich in diverse classes of ciliary membrane proteins. In
    MeSH term(s) Animals ; Chlamydomonas reinhardtii/metabolism ; Cilia/metabolism ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; Protein Binding ; Protein Transport
    Chemical Substances Cytoskeletal Proteins ; Intracellular Signaling Peptides and Proteins ; WDR35 protein, mouse
    Language English
    Publishing date 2021-11-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.69786
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  9. Article ; Online: The effect of Dnaaf5 gene dosage on primary ciliary dyskinesia phenotypes.

    Horani, Amjad / Gupta, Deepesh Kumar / Xu, Jian / Xu, Huihui / Carmen Puga-Molina, Lis Del / Santi, Celia M / Ramagiri, Sruthi / Brennan, Steven K / Pan, Jiehong / Koenitzer, Jeffrey R / Huang, Tao / Hyland, Rachael M / Gunsten, Sean P / Tzeng, Shin-Cheng / Strahle, Jennifer M / Mill, Pleasantine / Mahjoub, Moe R / Dutcher, Susan K / Brody, Steven L

    JCI insight

    2023  Volume 8, Issue 11

    Abstract: DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 ... ...

    Abstract DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift-null deletion in Dnaaf5. Litters with Dnaaf5 heteroallelic variants showed distinct missense and null gene dosage effects. Homozygosity for the null Dnaaf5 alleles was embryonic lethal. Compound heterozygous animals with the missense and null alleles showed severe disease manifesting as hydrocephalus and early lethality. However, animals homozygous for the missense mutation had improved survival, with partially preserved cilia function and motor assembly observed by ultrastructure analysis. Notably, the same variant alleles exhibited divergent cilia function across different multiciliated tissues. Proteomic analysis of isolated airway cilia from mutant mice revealed reduction in some axonemal regulatory and structural proteins not previously reported in DNAAF5 variants. Transcriptional analysis of mouse and human mutant cells showed increased expression of genes coding for axonemal proteins. These findings suggest allele-specific and tissue-specific molecular requirements for cilia motor assembly that may affect disease phenotypes and clinical trajectory in motile ciliopathies.
    MeSH term(s) Animals ; Humans ; Kartagener Syndrome/genetics ; Proteomics ; Mutation ; Phenotype ; Proteins/genetics ; Gene Dosage
    Chemical Substances Proteins
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.168836
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  10. Article ; Online: Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function.

    Haward, Fiona / Maslon, Magdalena M / Yeyati, Patricia L / Bellora, Nicolas / Hansen, Jan N / Aitken, Stuart / Lawson, Jennifer / von Kriegsheim, Alex / Wachten, Dagmar / Mill, Pleasantine / Adams, Ian R / Caceres, Javier F

    eLife

    2021  Volume 10

    Abstract: Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. The SR family proteins regulate RNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post- ... ...

    Abstract Shuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. The SR family proteins regulate RNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in
    MeSH term(s) Animals ; Cell Nucleus/metabolism ; Cilia/metabolism ; Cytoplasm/metabolism ; Male ; Mice ; Serine-Arginine Splicing Factors/genetics ; Serine-Arginine Splicing Factors/metabolism
    Chemical Substances Srsf1 protein, mouse ; Serine-Arginine Splicing Factors (170974-22-8)
    Language English
    Publishing date 2021-08-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.65104
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