Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo Journal Article
| Authors: | Ocbina, P. J. R.; Tuson, M.; Anderson, K. V. |
| Article Title: | Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo |
| Abstract: | Background: Sonic hedgehog (Shh) signaling in the mouse requires the microtubule-based organelle, the primary cilium. The primary cilium is assembled and maintained through the process of intraflagellar transport (IFT) and the response to Shh is blocked in mouse mutants that lack proteins required for IFT. Although the phenotypes of mouse IFT mutants do not overlap with phenotypes of known Wnt pathway mutants, recent studies report data suggesting that the primary cilium modulates responses to Wnt signals. Methodology/Principal Findings: We therefore carried out a systematic analysis of canonical Wnt signaling in mutant embryos and cells that lack primary cilia because of loss of the anterograde IFT kinesin-II motor (Kif3a) or IFT complex B proteins (Ift172 or Ift88). We also analyzed mutant embryos with abnormal primary cilia due to defects in retrograde IFT (Dync2h1). The mouse IFT mutants express the canonical Wnt target Axin2 and activate a transgenic canonical Wnt reporter, BAT-gal, in the normal spatial pattern and to the same quantitative level as wild type littermates. Similarly, mouse embryonic fibroblasts (MEFs) derived from IFT mutants respond normally to added Wnt3a. The switch from canonical to non-canonical Wnt also appears normal in IFT mutant MEFs, as both wild-type and mutant cells do not activate the canonical Wnt reporter in the presence of both Wnt3a and Wnt5a. Conclusions: We conclude that loss of primary cilia or defects in retrograde IFT do not affect the response of the midgestation embryo or embryo-derived fibroblasts to Wnt ligands. © 2009 Ocbina et al. |
| Keywords: | signal transduction; controlled study; protein expression; carrier protein; unclassified drug; nonhuman; animal cell; mouse; animal; metabolism; animals; mice; cells, cultured; embryo; protein targeting; wild type; physiology; cell culture; fibroblast; cell transport; wnt proteins; wnt protein; erinaceidae; eukaryotic flagellum; cilia; cell mutant; intraflagellar transport; axin; axin 2; intraflagellar transport protein 172; intraflagellar transport protein 88; kinesin 2; protein dync2h1; protein kif3a; wnt3a protein; wnt5a protein; embryo cell |
| Journal Title: | PLoS ONE |
| Volume: | 4 |
| Issue: | 8 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2009-08-31 |
| Start Page: | e6839 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0006839 |
| PUBMED: | 19718259 |
| PROVIDER: | scopus |
| PMCID: | PMC2729396 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 13" - "Export Date: 30 November 2010" - "Art. No.: e6839" - "Source: Scopus" |
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