Hedgehog Signalling in the Mouse Requires Intraflagellar Transport Proteins

Nature. 2003 Nov 6;426(6962):83-7. doi: 10.1038/nature02061.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Biological Transport
  • Body Patterning*
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Female
  • Flagella / metabolism*
  • Hedgehog Proteins
  • Intracellular Signaling Peptides and Proteins*
  • Kinesin / genetics
  • Kinesin / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins*
  • Nervous System / embryology
  • Nervous System / metabolism
  • Neurons / metabolism
  • Patched Receptors
  • Patched-1 Receptor
  • Phenotype
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptors, Cell Surface
  • Signal Transduction*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Suppressor Proteins*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Hedgehog Proteins
  • Ift172 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Kif3a protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Patched Receptors
  • Patched-1 Receptor
  • Proteins
  • Ptch1 protein, mouse
  • Receptors, Cell Surface
  • Tg737Rpw protein, mouse
  • Trans-Activators
  • Tumor Suppressor Proteins
  • osm-5 protein, C elegans
  • ptc-1 protein, C elegans
  • Kinesin

Associated data

  • GENBANK/AY339616