The graded response to Sonic Hedgehog depends on cilia architecture

Dev Cell. 2007 May;12(5):767-78. doi: 10.1016/j.devcel.2007.03.004.


Several studies have linked cilia and Hedgehog signaling, but the precise roles of ciliary proteins in signal transduction remain enigmatic. Here we describe a mouse mutation, hennin (hnn), that causes coupled defects in cilia structure and Sonic hedgehog (Shh) signaling. The hnn mutant cilia are short with a specific defect in the structure of the ciliary axoneme, and the hnn neural tube shows a Shh-independent expansion of the domain of motor neuron progenitors. The hnn mutation is a null allele of Arl13b, a small GTPase of the Arf/Arl family, and the Arl13b protein is localized to cilia. Double mutant analysis indicates that Gli3 repressor activity is normal in hnn embryos, but Gli activators are constitutively active at low levels. Thus, normal structure of the ciliary axoneme is required for the cell to translate different levels of Shh ligand into differential regulation of the Gli transcription factors that implement Hedgehog signals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Body Patterning
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Cytoskeletal Proteins / metabolism
  • Embryo, Mammalian / abnormalities
  • Embryo, Mammalian / ultrastructure
  • Exons / genetics
  • Eye Abnormalities / embryology
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Introns / genetics
  • Ligands
  • Limb Deformities, Congenital / embryology
  • Mice
  • Mutation / genetics
  • Neural Tube Defects / embryology
  • Oncogene Proteins / metabolism
  • Patched Receptors
  • Phenotype
  • Protein Transport
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Smoothened Receptor
  • Trans-Activators / metabolism
  • Zinc Finger Protein GLI1


  • Cytoskeletal Proteins
  • Hedgehog Proteins
  • Ligands
  • Oncogene Proteins
  • Patched Receptors
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Shh protein, mouse
  • Smo protein, mouse
  • Smoothened Receptor
  • Trans-Activators
  • Zinc Finger Protein GLI1