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Intraflagellar transport, cilia, and mammalian Hedgehog signaling: Analysis in mouse embryonic fibroblasts
Author(s) -
Ocbina Polloneal Jymmiel R.,
Anderson Kathryn V.
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21551
Subject(s) - intraflagellar transport , cilium , hedgehog , smoothened , microbiology and biotechnology , biology , hedgehog signaling pathway , sonic hedgehog , signal transduction , embryonic stem cell , mutant , wild type , patched , genetics , gene
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. Developmental Dynamics 237:2030–2038, 2008. © 2008 Wiley‐Liss, Inc.