Intraflagellar transport, Cilia, and mammalian hedgehog signaling: Analysis in mouse embryonic fibroblasts Journal Article


Authors: Ocbina, P. J. R.; Anderson, K. V.
Article Title: Intraflagellar transport, Cilia, and mammalian hedgehog signaling: Analysis in mouse embryonic fibroblasts
Abstract: Genetic studies in the mouse have shown that Intraflagellar Transport (IFT) is essential for mammalian Hedgehog (Hh) signal transduction. In this study, we take advantage of wild type and IFT mutant mouse embryonic fibroblasts (MEFs) to characterize additional aspects of the relationship between IFT and Hh signaling. Exposure to Sonic hedgehog (Shh) ligand or expression of an activated allele of Smo, SmoA1, activates an Hh reporter in wild-type MEFs, but not in MEFs derived from embryos that lack IFT172 or the Dync2h1 subunit of the retrograde IFT motor. Similarly, decreased activity of either Sufu or PKA, two negative regulators of Hh signal transduction, activates the pathway in wild-type, but not IFT mutant, MEFs. In contrast to wild-type MEFs, Smo is constitutively present in the cilia of Dync2h1 mutant MEFs. This finding suggests that IFT-dependent trafficking of Hh pathway components through the cilium is essential for their function. © 2008 Wiley-Liss, Inc.
Keywords: signal transduction; protein expression; nonhuman; protein function; animal cell; mouse; mammalia; animals; mice; allele; embryo; sonic hedgehog protein; hedgehog proteins; mice, mutant strains; wild type; gene expression regulation, developmental; intracellular signaling peptides and proteins; fibroblast; fibroblasts; fetus; protein kinase a; cell transport; luciferases; enzyme subunit; repressor proteins; erinaceidae; smoothened protein; receptors, g-protein-coupled; cilia; ligand binding; biological transport; embryo culture; smoothened; ciliary motility; flagella; embryo cell; cyclic amp dependent protein kinase; cyclic amp-dependent protein kinases; cytoplasmic dynein; microscopy, electron, scanning; dync2h1; ift172; suppressor of fused; flagellum
Journal Title: Developmental Dynamics
Volume: 237
Issue: 8
ISSN: 1058-8388
Publisher: Wiley Periodicals, Inc  
Date Published: 2008-08-01
Start Page: 2030
End Page: 2038
Language: English
DOI: 10.1002/dvdy.21551
PUBMED: 18488998
PROVIDER: scopus
PMCID: PMC2702862
DOI/URL:
Notes: --- - "Cited By (since 1996): 42" - "Export Date: 17 November 2011" - "CODEN: DEDYE" - "Source: Scopus"
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  1. Kathryn Anderson
    148 Anderson
  2. Polloneal Jymmiel Ocbina
    8 Ocbina