The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation

Yili Yin, Fiona Bangs, I. Robert Paton, Alan Prescott, John James, Megan G. Davey, Paul Whitley, Grigory Genikhovich, Ulrich Technau, David W. Burt, Cheryll Tickle

    Research output: Contribution to journalArticle

    81 Citations (Scopus)

    Abstract

    The chicken talpid(3) mutant, with polydactyly and defects in other embryonic regions that depend on hedgehog (Hh) signalling ( e. g. the neural tube), has a mutation in KIAA0568. Similar phenotypes are seen in mice and in human syndromes with mutations in genes that encode centrosomal or intraflagella transport proteins. Such mutations lead to defects in primary cilia, sites where Hh signalling occurs. Here, we show that cells of talpid(3) mutant embryos lack primary cilia and that primary cilia can be rescued with constructs encoding Talpid3. talpid(3) mutant embryos also develop polycystic kidneys, consistent with widespread failure of ciliogenesis. Ultrastructural studies of talpid(3) mutant neural tube show that basal bodies mature but fail to dock with the apical cell membrane, are misorientated and almost completely lack ciliary axonemes. We also detected marked changes in actin organisation in talpid(3) mutant cells, which may explain misorientation of basal bodies. KIAA0586 was identified in the human centrosomal proteome and, using an antibody against chicken Talpid3, we detected Talpid3 in the centrosome of wild-type chicken cells but not in mutant cells. Cloning and bioinformatic analysis of the Talpid3 homolog from the sea anemone Nematostella vectensis identified a highly conserved region in the Talpid3 protein, including a predicted coiled-coil domain. We show that this region is required to rescue primary cilia formation and neural tube patterning in talpid(3) mutant embryos, and is sufficient for centrosomal localisation. Thus, Talpid3 is one of a growing number of centrosomal proteins that affect both ciliogenesis and Hh signalling.

    Original languageEnglish
    Pages (from-to)655-664
    Number of pages10
    JournalDevelopment
    Volume136
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2009

    Keywords

    • Primary cilia
    • Centrosome
    • Hedgehog signalling
    • Ciliopathies
    • Talpid3
    • Chicken
    • Neural tube
    • Embryo
    • BARDET-BIEDL-SYNDROME
    • DEVELOPMENTAL ABNORMALITIES
    • INTRAFLAGELLAR TRANSPORT
    • EPITHELIAL-CELLS
    • BODY PROTEIN
    • SHH PATHWAY
    • LIMB-BUD
    • HEDGEHOG
    • DISEASE
    • MUTANT

    Cite this

    Yin, Yili ; Bangs, Fiona ; Paton, I. Robert ; Prescott, Alan ; James, John ; Davey, Megan G. ; Whitley, Paul ; Genikhovich, Grigory ; Technau, Ulrich ; Burt, David W. ; Tickle, Cheryll. / The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation. In: Development. 2009 ; Vol. 136, No. 4. pp. 655-664.
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    title = "The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation",
    abstract = "The chicken talpid(3) mutant, with polydactyly and defects in other embryonic regions that depend on hedgehog (Hh) signalling ( e. g. the neural tube), has a mutation in KIAA0568. Similar phenotypes are seen in mice and in human syndromes with mutations in genes that encode centrosomal or intraflagella transport proteins. Such mutations lead to defects in primary cilia, sites where Hh signalling occurs. Here, we show that cells of talpid(3) mutant embryos lack primary cilia and that primary cilia can be rescued with constructs encoding Talpid3. talpid(3) mutant embryos also develop polycystic kidneys, consistent with widespread failure of ciliogenesis. Ultrastructural studies of talpid(3) mutant neural tube show that basal bodies mature but fail to dock with the apical cell membrane, are misorientated and almost completely lack ciliary axonemes. We also detected marked changes in actin organisation in talpid(3) mutant cells, which may explain misorientation of basal bodies. KIAA0586 was identified in the human centrosomal proteome and, using an antibody against chicken Talpid3, we detected Talpid3 in the centrosome of wild-type chicken cells but not in mutant cells. Cloning and bioinformatic analysis of the Talpid3 homolog from the sea anemone Nematostella vectensis identified a highly conserved region in the Talpid3 protein, including a predicted coiled-coil domain. We show that this region is required to rescue primary cilia formation and neural tube patterning in talpid(3) mutant embryos, and is sufficient for centrosomal localisation. Thus, Talpid3 is one of a growing number of centrosomal proteins that affect both ciliogenesis and Hh signalling.",
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    author = "Yili Yin and Fiona Bangs and Paton, {I. Robert} and Alan Prescott and John James and Davey, {Megan G.} and Paul Whitley and Grigory Genikhovich and Ulrich Technau and Burt, {David W.} and Cheryll Tickle",
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    Yin, Y, Bangs, F, Paton, IR, Prescott, A, James, J, Davey, MG, Whitley, P, Genikhovich, G, Technau, U, Burt, DW & Tickle, C 2009, 'The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation', Development, vol. 136, no. 4, pp. 655-664. https://doi.org/10.1242/dev.028464

    The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation. / Yin, Yili; Bangs, Fiona; Paton, I. Robert; Prescott, Alan; James, John; Davey, Megan G.; Whitley, Paul; Genikhovich, Grigory; Technau, Ulrich; Burt, David W.; Tickle, Cheryll.

    In: Development, Vol. 136, No. 4, 15.02.2009, p. 655-664.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation

    AU - Yin, Yili

    AU - Bangs, Fiona

    AU - Paton, I. Robert

    AU - Prescott, Alan

    AU - James, John

    AU - Davey, Megan G.

    AU - Whitley, Paul

    AU - Genikhovich, Grigory

    AU - Technau, Ulrich

    AU - Burt, David W.

    AU - Tickle, Cheryll

    PY - 2009/2/15

    Y1 - 2009/2/15

    N2 - The chicken talpid(3) mutant, with polydactyly and defects in other embryonic regions that depend on hedgehog (Hh) signalling ( e. g. the neural tube), has a mutation in KIAA0568. Similar phenotypes are seen in mice and in human syndromes with mutations in genes that encode centrosomal or intraflagella transport proteins. Such mutations lead to defects in primary cilia, sites where Hh signalling occurs. Here, we show that cells of talpid(3) mutant embryos lack primary cilia and that primary cilia can be rescued with constructs encoding Talpid3. talpid(3) mutant embryos also develop polycystic kidneys, consistent with widespread failure of ciliogenesis. Ultrastructural studies of talpid(3) mutant neural tube show that basal bodies mature but fail to dock with the apical cell membrane, are misorientated and almost completely lack ciliary axonemes. We also detected marked changes in actin organisation in talpid(3) mutant cells, which may explain misorientation of basal bodies. KIAA0586 was identified in the human centrosomal proteome and, using an antibody against chicken Talpid3, we detected Talpid3 in the centrosome of wild-type chicken cells but not in mutant cells. Cloning and bioinformatic analysis of the Talpid3 homolog from the sea anemone Nematostella vectensis identified a highly conserved region in the Talpid3 protein, including a predicted coiled-coil domain. We show that this region is required to rescue primary cilia formation and neural tube patterning in talpid(3) mutant embryos, and is sufficient for centrosomal localisation. Thus, Talpid3 is one of a growing number of centrosomal proteins that affect both ciliogenesis and Hh signalling.

    AB - The chicken talpid(3) mutant, with polydactyly and defects in other embryonic regions that depend on hedgehog (Hh) signalling ( e. g. the neural tube), has a mutation in KIAA0568. Similar phenotypes are seen in mice and in human syndromes with mutations in genes that encode centrosomal or intraflagella transport proteins. Such mutations lead to defects in primary cilia, sites where Hh signalling occurs. Here, we show that cells of talpid(3) mutant embryos lack primary cilia and that primary cilia can be rescued with constructs encoding Talpid3. talpid(3) mutant embryos also develop polycystic kidneys, consistent with widespread failure of ciliogenesis. Ultrastructural studies of talpid(3) mutant neural tube show that basal bodies mature but fail to dock with the apical cell membrane, are misorientated and almost completely lack ciliary axonemes. We also detected marked changes in actin organisation in talpid(3) mutant cells, which may explain misorientation of basal bodies. KIAA0586 was identified in the human centrosomal proteome and, using an antibody against chicken Talpid3, we detected Talpid3 in the centrosome of wild-type chicken cells but not in mutant cells. Cloning and bioinformatic analysis of the Talpid3 homolog from the sea anemone Nematostella vectensis identified a highly conserved region in the Talpid3 protein, including a predicted coiled-coil domain. We show that this region is required to rescue primary cilia formation and neural tube patterning in talpid(3) mutant embryos, and is sufficient for centrosomal localisation. Thus, Talpid3 is one of a growing number of centrosomal proteins that affect both ciliogenesis and Hh signalling.

    KW - Primary cilia

    KW - Centrosome

    KW - Hedgehog signalling

    KW - Ciliopathies

    KW - Talpid3

    KW - Chicken

    KW - Neural tube

    KW - Embryo

    KW - BARDET-BIEDL-SYNDROME

    KW - DEVELOPMENTAL ABNORMALITIES

    KW - INTRAFLAGELLAR TRANSPORT

    KW - EPITHELIAL-CELLS

    KW - BODY PROTEIN

    KW - SHH PATHWAY

    KW - LIMB-BUD

    KW - HEDGEHOG

    KW - DISEASE

    KW - MUTANT

    U2 - 10.1242/dev.028464

    DO - 10.1242/dev.028464

    M3 - Article

    VL - 136

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    JO - Development

    JF - Development

    SN - 0950-1991

    IS - 4

    ER -