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First published online 14 January 2009
doi: 10.1242/dev.028464

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

Yili Yin^1,*, Fiona Bangs^2,*, I. Robert Paton³, Alan Prescott⁴, John James⁴, Megan G. Davey³, Paul Whitley², Grigory Genikhovich⁵, Ulrich Technau⁵, David W. Burt³ and Cheryll Tickle^2,

¹ Division of Cell and Developmental Biology, Wellcome Trust Biocentre, The University of Dundee, Dundee DD1 5EH, UK.
² Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
³ Department of Genetics and Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian EH25 9PS, UK.
⁴ Centre for High Resolution Imaging and Processing, The University of Dundee, Dundee DD1 5EH, UK.
⁵ Developmental Biology Section, Faculty for Life Sciences, University of Vienna, Althanstrasse 14, 1090 Wien, Austria.

Author for correspondence (e-mail: cat24{at}bath.ac.uk)

Accepted 11 December 2008

The chicken talpid³ 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 talpid³ mutant embryos lack primary cilia and that primary cilia can be rescued with constructs encoding Talpid3. talpid³ mutant embryos also develop polycystic kidneys, consistent with widespread failure of ciliogenesis. Ultrastructural studies of talpid³ 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 talpid³ 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 talpid³ 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.

Key words: Primary cilia, Centrosome, Hedgehog signalling, Ciliopathies, Talpid3, Chicken, Neural tube, Embryo

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