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

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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.
LanguageEnglish
Pages655-664
Number of pages10
JournalDevelopment
Volume136
Issue number4
DOIs
StatusPublished - 2009

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Cilia
Neural Tube
Hedgehogs
Basal Bodies
Chickens
Embryonic Structures
Mutation
Genes
Proteins
Sea Anemones
Axoneme
Polydactyly
Polycystic Kidney Diseases
Centrosome
Proteome
Computational Biology
Actins
Organism Cloning
Carrier Proteins
Cell Membrane

Keywords

  • Embryo
  • Chicken
  • Primary cilia
  • Neural tube
  • Talpid3
  • Centrosome
  • Ciliopathies
  • Hedgehog signalling

Cite this

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, 2009, p. 655-664.

Research output: Contribution to journalArticle

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. DOI: 10.1242/dev.028464
Yin Y, Bangs F, Paton IR, Prescott A, James J, Davey MG et al. The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation. Development. 2009;136(4):655-664. Available from, DOI: 10.1242/dev.028464
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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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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T1 - The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation

AU - Yin,Yili

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AU - Paton,I. Robert

AU - Prescott,Alan

AU - James,John

AU - Davey,Megan G.

AU - Whitley,Paul

AU - Genikhovich,Grigory

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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.

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