Hedgehog signalling in the mouse requires intraflagellar transport proteins Journal Article
| Authors: | Huangfu, D.; Liu, A.; Rakeman, A. S.; Murcia, N. S.; Niswander, L.; Anderson, K. V. |
| Article Title: | Hedgehog signalling in the mouse requires intraflagellar transport proteins |
| Abstract: | Intraflagellar transport (IFT) proteins were first identified as essential factors for the growth and maintenance of flagella in the single-celled alga Chlamydomonas reinhardtii. In a screen for embryonic patterning mutations induced by ethylnitrosourea, here we identify two mouse mutants, wimple (wim) and flexo (fxo), that lack ventral neural cell types and show other phenotypes characteristic of defects in Sonic hedgehog signalling. Both mutations disrupt IFT proteins: the wim mutation is an allele of the previously uncharacterized mouse homologue of IFT172; and fxo is a new hypomorphic allele of polaris, the mouse homologue of IFT88. Genetic analysis shows that Wim, Polaris and the IFT motor protein Kif3a are required for Hedgehog signalling at a step downstream of Patched1 (the Hedgehog receptor) and upstream of direct targets of Hedgehog signalling. Our data show that IFT machinery has an essential and vertebrate-specific role in Hedgehog signal transduction. |
| Keywords: | signal transduction; carrier protein; unclassified drug; mutation; nonhuman; mutant protein; genetic analysis; proteins; protein analysis; mouse; phenotype; mammalia; animals; mice; allele; biology; embryo; sonic hedgehog protein; hedgehog proteins; mice, mutant strains; nerve tissue proteins; protein; membrane proteins; alleles; neurons; animalia; vertebrata; gene mapping; molecular sequence data; intracellular signaling peptides and proteins; carrier proteins; tumor suppressor proteins; trans-activators; animal cell culture; biochemistry; nerve cell; erinaceidae; body patterning; ethylnitrosourea; mutagenesis; biological transport; flagella; kinesin; mutations; receptors, cell surface; nervous system; mutants; caenorhabditis elegans proteins; hedgehog; chlamydomonas; flagellum; growth kinetics; algae; alga; male; female; priority journal; article; transport properties; bioreceptors; protein fxo; protein ift; protein wim; chlamydomonas reinhardtii |
| Journal Title: | Nature |
| Volume: | 426 |
| Issue: | 6962 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2003-11-06 |
| Start Page: | 83 |
| End Page: | 87 |
| Language: | English |
| DOI: | 10.1038/nature02061 |
| PUBMED: | 14603322 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Molecular Sequence Numbers: GENBANK: AY339616; -- Source: Scopus |
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