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Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis

Author

Listed:
  • Shobi Veleri

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

  • Souparnika H. Manjunath

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

  • Robert N. Fariss

    (Biological Imaging Core, National Eye Institute, NIH)

  • Helen May-Simera

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

  • Matthew Brooks

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

  • Trevor A. Foskett

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

  • Chun Gao

    (Biological Imaging Core, National Eye Institute, NIH)

  • Teresa A. Longo

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

  • Pinghu Liu

    (Genetic Engineering Core, National Eye Institute, NIH)

  • Kunio Nagashima

    (Electron Microscope Laboratory, Advanced Technology Program, Frederick National Laboratory for Cancer Research)

  • Rivka A. Rachel

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

  • Tiansen Li

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

  • Lijin Dong

    (Genetic Engineering Core, National Eye Institute, NIH)

  • Anand Swaroop

    (Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH)

Abstract

The primary cilium originates from the mother centriole and participates in critical functions during organogenesis. Defects in cilia biogenesis or function lead to pleiotropic phenotypes. Mutations in centrosome-cilia gene CC2D2A result in Meckel and Joubert syndromes. Here we generate a Cc2d2a−/− mouse that recapitulates features of Meckel syndrome including embryonic lethality and multiorgan defects. Cilia are absent in Cc2d2a−/− embryonic node and other somatic tissues; disruption of cilia-dependent Shh signalling appears to underlie exencephaly in mutant embryos. The Cc2d2a−/− mouse embryonic fibroblasts (MEFs) lack cilia, although mother centrioles and pericentriolar proteins are detected. Odf2, associated with subdistal appendages, is absent and ninein is reduced in mutant MEFs. In Cc2d2a−/− MEFs, subdistal appendages are lacking or abnormal by transmission electron microscopy. Consistent with this, CC2D2A localizes to subdistal appendages by immuno-EM in wild-type cells. We conclude that CC2D2A is essential for the assembly of subdistal appendages, which anchor cytoplasmic microtubules and prime the mother centriole for axoneme biogenesis.

Suggested Citation

  • Shobi Veleri & Souparnika H. Manjunath & Robert N. Fariss & Helen May-Simera & Matthew Brooks & Trevor A. Foskett & Chun Gao & Teresa A. Longo & Pinghu Liu & Kunio Nagashima & Rivka A. Rachel & Tianse, 2014. "Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5207
    DOI: 10.1038/ncomms5207
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