期刊
DEVELOPMENTAL DYNAMICS
卷 237, 期 8, 页码 2030-2038出版社
WILEY-BLACKWELL
DOI: 10.1002/dvdy.21551
关键词
Dync2h1; IFT172; Smoothened; Suppressor of fused; protein kinase a; cytoplasmic dynein
资金
- NINDS NIH HHS [R01 NS044385-01, R01 NS044385, R01 NS044385-04, R01 NS044385-03, R01 NS044385-06, R01 NS044385-02, R01 NS044385-05, R01 NS044385-07] Funding Source: Medline
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.
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