LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article ; Online: Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo.

    Ocbina, Polloneal Jymmiel R / Tuson, Miquel / Anderson, Kathryn V

    PloS one

    2009  Volume 4, Issue 8, Page(s) e6839

    Abstract: Background: Sonic hedgehog (Shh) signaling in the mouse requires the microtubule-based organelle, the primary cilium. The primary cilium is assembled and maintained through the process of intraflagellar transport (IFT) and the response to Shh is blocked ...

    Abstract Background: Sonic hedgehog (Shh) signaling in the mouse requires the microtubule-based organelle, the primary cilium. The primary cilium is assembled and maintained through the process of intraflagellar transport (IFT) and the response to Shh is blocked in mouse mutants that lack proteins required for IFT. Although the phenotypes of mouse IFT mutants do not overlap with phenotypes of known Wnt pathway mutants, recent studies report data suggesting that the primary cilium modulates responses to Wnt signals.
    Methodology/principal findings: We therefore carried out a systematic analysis of canonical Wnt signaling in mutant embryos and cells that lack primary cilia because of loss of the anterograde IFT kinesin-II motor (Kif3a) or IFT complex B proteins (Ift172 or Ift88). We also analyzed mutant embryos with abnormal primary cilia due to defects in retrograde IFT (Dync2h1). The mouse IFT mutants express the canonical Wnt target Axin2 and activate a transgenic canonical Wnt reporter, BAT-gal, in the normal spatial pattern and to the same quantitative level as wild type littermates. Similarly, mouse embryonic fibroblasts (MEFs) derived from IFT mutants respond normally to added Wnt3a. The switch from canonical to non-canonical Wnt also appears normal in IFT mutant MEFs, as both wild-type and mutant cells do not activate the canonical Wnt reporter in the presence of both Wnt3a and Wnt5a.
    Conclusions: We conclude that loss of primary cilia or defects in retrograde IFT do not affect the response of the midgestation embryo or embryo-derived fibroblasts to Wnt ligands.
    MeSH term(s) Animals ; Cells, Cultured ; Cilia/physiology ; Mice ; Signal Transduction/physiology ; Wnt Proteins/metabolism
    Chemical Substances Wnt Proteins
    Language English
    Publishing date 2009-08-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0006839
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Complex interactions between genes controlling trafficking in primary cilia.

    Ocbina, Polloneal Jymmiel R / Eggenschwiler, Jonathan T / Moskowitz, Ivan / Anderson, Kathryn V

    Nature genetics

    2011  Volume 43, Issue 6, Page(s) 547–553

    Abstract: Cilia-associated human genetic disorders are striking in the diversity of their abnormalities and their complex inheritance. Inactivation of the retrograde ciliary motor by mutations in DYNC2H1 causes skeletal dysplasias that have strongly variable ... ...

    Abstract Cilia-associated human genetic disorders are striking in the diversity of their abnormalities and their complex inheritance. Inactivation of the retrograde ciliary motor by mutations in DYNC2H1 causes skeletal dysplasias that have strongly variable expressivity. Here we define previously unknown genetic relationships between Dync2h1 and other genes required for ciliary trafficking. Mutations in mouse Dync2h1 disrupt cilia structure, block Sonic hedgehog signaling and cause midgestation lethality. Heterozygosity for Ift172, a gene required for anterograde ciliary trafficking, suppresses cilia phenotypes, Sonic hedgehog signaling defects and early lethality of Dync2h1 homozygotes. Ift122, like Dync2h1, is required for retrograde ciliary trafficking, but reduction of Ift122 gene dosage also suppresses the Dync2h1 phenotype. These genetic interactions illustrate the cell biology underlying ciliopathies and argue that mutations in intraflagellar transport genes cause their phenotypes because of their roles in cilia architecture rather than direct roles in signaling.
    MeSH term(s) Adaptor Proteins, Signal Transducing ; Animals ; Carrier Proteins/metabolism ; Cilia/genetics ; Cytoplasmic Dyneins/genetics ; Cytoskeletal Proteins ; Fibroblasts/metabolism ; Hedgehog Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/physiology ; Mice ; Mutation
    Chemical Substances Adaptor Proteins, Signal Transducing ; Carrier Proteins ; Cytoskeletal Proteins ; DYNC2H1 protein, human ; Hedgehog Proteins ; Ift122 protein, mouse ; Ift172 protein, mouse ; Intracellular Signaling Peptides and Proteins ; Shh protein, mouse ; Cytoplasmic Dyneins (EC 3.6.4.2)
    Language English
    Publishing date 2011-05-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.832
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3613: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 46: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: Intraflagellar transport, cilia, and mammalian Hedgehog signaling: analysis in mouse embryonic fibroblasts.

    Ocbina, Polloneal Jymmiel R / Anderson, Kathryn V

    Developmental dynamics : an official publication of the American Association of Anatomists

    2008  Volume 237, Issue 8, Page(s) 2030–2038

    Abstract: Genetic studies in the mouse have shown that Intraflagellar Transport (IFT) is essential for mammalian Hedgehog (Hh) signal transduction. In this study, we take advantage of wild type and IFT mutant mouse embryonic fibroblasts (MEFs) to characterize ... ...

    Abstract Genetic studies in the mouse have shown that Intraflagellar Transport (IFT) is essential for mammalian Hedgehog (Hh) signal transduction. In this study, we take advantage of wild type and IFT mutant mouse embryonic fibroblasts (MEFs) to characterize additional aspects of the relationship between IFT and Hh signaling. Exposure to Sonic hedgehog (Shh) ligand or expression of an activated allele of Smo, SmoA1, activates an Hh reporter in wild-type MEFs, but not in MEFs derived from embryos that lack IFT172 or the Dync2h1 subunit of the retrograde IFT motor. Similarly, decreased activity of either Sufu or PKA, two negative regulators of Hh signal transduction, activates the pathway in wild-type, but not IFT mutant, MEFs. In contrast to wild-type MEFs, Smo is constitutively present in the cilia of Dync2h1 mutant MEFs. This finding suggests that IFT-dependent trafficking of Hh pathway components through the cilium is essential for their function.
    MeSH term(s) Adaptor Proteins, Signal Transducing ; Animals ; Biological Transport/physiology ; Cilia/metabolism ; Cilia/ultrastructure ; Cyclic AMP-Dependent Protein Kinases/genetics ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytoskeletal Proteins ; Fetus/cytology ; Fibroblasts/metabolism ; Fibroblasts/ultrastructure ; Flagella/metabolism ; Gene Expression Regulation, Developmental ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Luciferases/genetics ; Mice ; Mice, Mutant Strains ; Microscopy, Electron, Scanning ; Receptors, G-Protein-Coupled/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Signal Transduction/physiology ; Smoothened Receptor
    Chemical Substances Adaptor Proteins, Signal Transducing ; Cytoskeletal Proteins ; Hedgehog Proteins ; Ift172 protein, mouse ; Intracellular Signaling Peptides and Proteins ; Receptors, G-Protein-Coupled ; Repressor Proteins ; Shh protein, mouse ; Smo protein, mouse ; Smoothened Receptor ; Sufu protein, mouse ; Luciferases (EC 1.13.12.-) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11)
    Language English
    Publishing date 2008-05-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1102541-4
    ISSN 1097-0177 ; 1058-8388
    ISSN (online) 1097-0177
    ISSN 1058-8388
    DOI 10.1002/dvdy.21551
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ub I Zs.60: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 64: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling.

    Liem, Karel F / He, Mu / Ocbina, Polloneal Jymmiel R / Anderson, Kathryn V

    Proceedings of the National Academy of Sciences of the United States of America

    2009  Volume 106, Issue 32, Page(s) 13377–13382

    Abstract: Mammalian Sonic hedgehog (Shh) signaling is essential for embryonic development and stem cell maintenance and has critical roles in tumorigenesis. Although core components of the Shh pathway are conserved in evolution, important aspects of mammalian Shh ... ...

    Abstract Mammalian Sonic hedgehog (Shh) signaling is essential for embryonic development and stem cell maintenance and has critical roles in tumorigenesis. Although core components of the Shh pathway are conserved in evolution, important aspects of mammalian Shh signaling are not shared with the Drosophila pathway. Perhaps the most dramatic difference between the Drosophila and mammalian pathways is that Shh signaling in the mouse requires a microtubule-based organelle, the primary cilium. Proteins that are required for the response to Shh are enriched in the cilium, but it is not clear why the cilium provides an appropriate venue for signal transduction. Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factors. By using a Kif7 mutant allele identified in a reporter-based genetic screen, we show that, similar to Drosophila and zebrafish Cos2, mouse Kif7 acts downstream of Smo and upstream of Gli2 and has both negative and positive roles in Shh signal transduction. Mouse Kif7 activity depends on the presence of cilia and Kif7-eGFP localizes to base of the primary cilium in the absence of Shh. Activation of the Shh pathway promotes trafficking of Kif7-eGFP from the base to the tip of the cilium, and localization to the tip of the cilium is disrupted in a motor domain mutant. We conclude that Kif7 is a core regulator of Shh signaling that may also act as a ciliary motor.
    MeSH term(s) Animals ; Cell Lineage ; Cilia/metabolism ; Flagella/metabolism ; Hedgehog Proteins/metabolism ; Kinesin/genetics ; Kinesin/metabolism ; Mice ; Mutation/genetics ; Neural Tube/cytology ; Neural Tube/metabolism ; Phenotype ; Protein Transport ; Signal Transduction
    Chemical Substances Hedgehog Proteins ; Shh protein, mouse ; Kif7 protein, mouse (EC 3.6.1.-) ; Kinesin (EC 3.6.4.4)
    Language English
    Publishing date 2009-07-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0906944106
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article: Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling

    Liem, Karel F. Jr / He, Mu / Ocbina, Polloneal Jymmiel R / Anderson, Kathryn V

    Proceedings of the National Academy of Sciences of the United States of America. 2009 Aug. 11, v. 106, no. 32

    2009  

    Abstract: Mammalian Sonic hedgehog (Shh) signaling is essential for embryonic development and stem cell maintenance and has critical roles in tumorigenesis. Although core components of the Shh pathway are conserved in evolution, important aspects of mammalian Shh ... ...

    Abstract Mammalian Sonic hedgehog (Shh) signaling is essential for embryonic development and stem cell maintenance and has critical roles in tumorigenesis. Although core components of the Shh pathway are conserved in evolution, important aspects of mammalian Shh signaling are not shared with the Drosophila pathway. Perhaps the most dramatic difference between the Drosophila and mammalian pathways is that Shh signaling in the mouse requires a microtubule-based organelle, the primary cilium. Proteins that are required for the response to Shh are enriched in the cilium, but it is not clear why the cilium provides an appropriate venue for signal transduction. Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factors. By using a Kif7 mutant allele identified in a reporter-based genetic screen, we show that, similar to Drosophila and zebrafish Cos2, mouse Kif7 acts downstream of Smo and upstream of Gli2 and has both negative and positive roles in Shh signal transduction. Mouse Kif7 activity depends on the presence of cilia and Kif7-eGFP localizes to base of the primary cilium in the absence of Shh. Activation of the Shh pathway promotes trafficking of Kif7-eGFP from the base to the tip of the cilium, and localization to the tip of the cilium is disrupted in a motor domain mutant. We conclude that Kif7 is a core regulator of Shh signaling that may also act as a ciliary motor.
    Keywords Danio rerio ; Drosophila ; alleles ; carcinogenesis ; cilia ; embryogenesis ; evolution ; membrane proteins ; mice ; mutants ; signal transduction ; stem cells ; transcription factors
    Language English
    Dates of publication 2009-0811
    Size p. 13377-13382.
    Publishing place National Academy of Sciences
    Document type Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0906944106
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 63/44: Show issues
    87/25270: Show issues
    Qa 4' 169/3: Show issues
    Z 8.7: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: A novel murine allele of Intraflagellar Transport Protein 172 causes a syndrome including VACTERL-like features with hydrocephalus.

    Friedland-Little, Joshua M / Hoffmann, Andrew D / Ocbina, Polloneal Jymmiel R / Peterson, Mike A / Bosman, Joshua D / Chen, Yan / Cheng, Steven Y / Anderson, Kathryn V / Moskowitz, Ivan P

    Human molecular genetics

    2011  Volume 20, Issue 19, Page(s) 3725–3737

    Abstract: The primary cilium is emerging as a crucial regulator of signaling pathways central to vertebrate development and human disease. We identified atrioventricular canal 1 (avc1), a mouse mutation that caused VACTERL association with hydrocephalus, or ... ...

    Abstract The primary cilium is emerging as a crucial regulator of signaling pathways central to vertebrate development and human disease. We identified atrioventricular canal 1 (avc1), a mouse mutation that caused VACTERL association with hydrocephalus, or VACTERL-H. We showed that avc1 is a hypomorphic mutation of intraflagellar transport protein 172 (Ift172), required for ciliogenesis and Hedgehog (Hh) signaling. Phenotypically, avc1 caused VACTERL-H but not abnormalities in left-right (L-R) axis formation. Avc1 resulted in structural cilia defects, including truncated cilia in vivo and in vitro. We observed a dose-dependent requirement for Ift172 in ciliogenesis using an allelic series generated with Ift172(avc1) and Ift172(wim), an Ift172 null allele: cilia were present on 42% of avc1 mouse embryonic fibroblast (MEF) and 28% of avc1/wim MEFs, in contrast to >90% of wild-type MEFs. Furthermore, quantitative cilium length analysis identified two specific cilium populations in mutant MEFS: a normal population with normal IFT and a truncated population, 50% of normal length, with disrupted IFT. Cells from wild-type embryos had predominantly full-length cilia, avc1 embryos, with Hh signaling abnormalities but not L-R abnormalities, had cilia equally divided between full-length and truncated, and avc1/wim embryos, with both Hh signaling and L-R abnormalities, were primarily truncated. Truncated Ift172 mutant cilia showed defects of the distal ciliary axoneme, including disrupted IFT88 localization and Hh-dependent Gli2 localization. We propose a model in which mutation of Ift172 results in a specific class of abnormal cilia, causing disrupted Hh signaling while maintaining L-R axis determination, and resulting in the VACTERL-H phenotype.
    MeSH term(s) Adaptor Proteins, Signal Transducing ; Alleles ; Anal Canal/abnormalities ; Anal Canal/embryology ; Anal Canal/metabolism ; Animals ; Cilia/genetics ; Cilia/metabolism ; Cytoskeletal Proteins ; Disease Models, Animal ; Esophagus/abnormalities ; Esophagus/embryology ; Esophagus/metabolism ; Heart Defects, Congenital/embryology ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/metabolism ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Humans ; Hydrocephalus/embryology ; Hydrocephalus/genetics ; Hydrocephalus/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Kidney/abnormalities ; Kidney/embryology ; Kidney/metabolism ; Limb Deformities, Congenital/embryology ; Limb Deformities, Congenital/genetics ; Limb Deformities, Congenital/metabolism ; Mice/genetics ; Mice/metabolism ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mutagenesis ; Mutation ; Protein Transport ; Signal Transduction/genetics ; Spine/abnormalities ; Spine/embryology ; Spine/metabolism ; Trachea/abnormalities ; Trachea/embryology ; Trachea/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; Cytoskeletal Proteins ; Hedgehog Proteins ; Ift172 protein, mouse ; Intracellular Signaling Peptides and Proteins ; Tg737Rpw protein, mouse ; Tumor Suppressor Proteins
    Language English
    Publishing date 2011-06-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108742-0
    ISSN 1460-2083 ; 0964-6906
    ISSN (online) 1460-2083
    ISSN 0964-6906
    DOI 10.1093/hmg/ddr241
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3469: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top