Work

Intraflagellar transport, cilia, and mammalian Hedgehog signaling: Analysis in mouse embryonic fibroblasts

Year: 2008

Type: article

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.

Source: Developmental Dynamics

DOI: 10.1002/dvdy.21551

Authors: Polloneal Jymmiel R. Ocbina, Kathryn V. Anderson

Institution: Cornell University

Language: English

Topic: Genetic and Kidney Cyst Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: bronze

Funders: Memorial Sloan-Kettering Cancer Center, National Institute of Neurological Disorders and Stroke

Award: Genetic Analysis of Mouse Nervous System Development