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Nat Commun. 2014 Jun 20;5:4207. doi: 10.1038/ncomms5207.

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

Author information

1
Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, Maryland 20892, USA.
2
Biological Imaging Core, National Eye Institute, NIH, Bethesda, Maryland 20892, USA.
3
Genetic Engineering Core, National Eye Institute, NIH, Bethesda, Maryland 20892, USA.
4
Electron Microscope Laboratory, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.

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.

PMID:
24947469
PMCID:
PMC4096663
DOI:
10.1038/ncomms5207
[Indexed for MEDLINE]
Free PMC Article

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