Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli

Dev Biol. 2005 Nov 15;287(2):378-89. doi: 10.1016/j.ydbio.2005.08.050. Epub 2005 Oct 17.


Sonic Hedgehog (Shh) signals are transduced into nuclear ratios of Gli transcriptional activator versus repressor. The initial part of this process is accomplished by Shh acting through Patched (Ptc) to regulate Smoothened (Smo) activity. The mechanisms by which Ptc regulates Smo, and Smo activity is transduced to processing of Gli proteins remain unclear. Recently, a forward genetic approach in mice identified a role for intraflagellar transport (IFT) genes in Shh signal transduction, downstream of Patched (Ptc) and Rab23. Here, we show that the retrograde motor for IFT is required in the mouse for the phenotypic expression of both Gli activator and repressor function and for effective proteolytic processing of Gli3. Furthermore, we show that the localization of Smo to primary cilia is disrupted in mutants. These data indicate that primary cilia act as specialized signal transduction organelles required for coupling Smo activity to the biochemical processing of Gli3 protein.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Dyneins / genetics
  • Dyneins / metabolism*
  • Extremities / embryology
  • Flagella / metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors / metabolism
  • Kruppel-Like Transcription Factors / physiology*
  • Mice
  • Microscopy, Electron, Scanning
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Prosencephalon / abnormalities
  • Prosencephalon / embryology
  • Protein Transport / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Smoothened Receptor
  • Spinal Cord / abnormalities
  • Spinal Cord / embryology
  • Trans-Activators / physiology
  • Zinc Finger Protein Gli3


  • Gli3 protein, mouse
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Molecular Motor Proteins
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Shh protein, mouse
  • Smo protein, mouse
  • Smoothened Receptor
  • Trans-Activators
  • Zinc Finger Protein Gli3
  • Dnchc2 protein, mouse
  • Dyneins