Cilia and Hedgehog responsiveness in the mouse Journal Article
| Authors: | Huangfu, D.; Anderson, K. V. |
| Article Title: | Cilia and Hedgehog responsiveness in the mouse |
| Abstract: | The intraflagellar transport (IFT) proteins Ift172/Wimple and Polaris/ift88 and the anterograde IFT motor kinesin-II are required for the production and maintenance of cilia. These proteins are also required for the activation of targets of the mouse Hedgehog (Hh) pathway by Gli transcription factors. The phenotypes of the IFT mutants, however, are not identical to mutants that lack Smoothened (Smo), an essential activator of the Hh pathway. We show here that mouse embryos that lack both Ift172 and Smo are identical to IftJ72 single mutants, which indicates that Ift172 acts downstream of Smo. Ift172 mutants have a weaker neural patterning phenotype than Smo mutants, because Ift172, but not Smo, is required for proteolytic processing of Gli3 to its repressor form. Dnchc2 and Kif3a, essential subunits of the retrograde and anterograde IFT motors, are also required for both formation of Gli activator and proteolytic processing of Gli3. As a result, IFT mutants display a loss of Hh signaling phenotype in the neural tube, where Gli activators play the major role in pattern formation, and a gain of Hh signaling phenotype in the limb, where Gli3 repressor plays the major role. Because both anterograde and retrograde IFT are essential for positive and negative responses to Hh, and because cilia are present on Hh responsive cells, it is likely that cilia act as organelles that are required for all activity of the mouse Hh pathway. © 2005 by The National Academy of Sciences of the USA. |
| Keywords: | signal transduction; carrier protein; unclassified drug; mutation; nonhuman; mutant protein; mouse; phenotype; animals; mice; embryo; protein degradation; sonic hedgehog protein; hedgehog proteins; embryo pattern formation; central nervous system; mice, transgenic; transcription factors; cloning, molecular; blotting, western; molecular sequence data; intracellular signaling peptides and proteins; nucleotide sequence; oncogene proteins; tumor suppressor proteins; base sequence; trans-activators; dna primers; repressor protein; erinaceidae; receptors, g-protein-coupled; transcription factor gli1; transcription factor gli3; eukaryotic flagellum; body patterning; cilia; biological transport; neural tube; intraflagellar transport; kinesin; chromosome mapping; dynein atpase; sequence analysis, dna; node; ift172; gli proteins; intraflagellar transport protein; molecular motor proteins; dnchc2; protein smo; nerve fiber transport; nerve tract; retrograde nerve fiber transport |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 102 |
| Issue: | 32 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2005-08-01 |
| Start Page: | 11325 |
| End Page: | 11330 |
| Language: | English |
| DOI: | 10.1073/pnas.0505328102 |
| PUBMED: | 16061793 |
| PROVIDER: | scopus |
| PMCID: | PMC1183606 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 291" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Molecular Sequence Numbers: GENBANK: NM_023024, DQ104402;" - "Source: Scopus" |
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