Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb Academic Article uri icon


MeSH Major

  • DNA-Binding Proteins
  • Limb Buds
  • Nerve Tissue Proteins
  • Protein Processing, Post-Translational
  • Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Xenopus Proteins


  • Ci/Gli zinc finger proteins mediate the transcriptional effects of Hedgehog protein signals. In Drosophila, Ci action as transcriptional repressor or activator is contingent upon Hedgehog-regulated, PKA-dependent proteolytic processing. We demonstrate that PKA-dependent processing of vertebrate Gli3 in developing limb similarly generates a potent repressor in a manner antagonized by apparent long-range signaling from posteriorly localized Sonic hedgehog protein. The resulting anterior/posterior Gli3 repressor gradient can be perturbed by mutations of Gli3 in human genetic syndromes or by misregulation of Gli3 processing in the chicken mutant talpid2, producing a range of limb patterning malformations. The high relative abundance and potency of Gli3 repressor suggest specialization of Gli3 and its products for negative Hedgehog pathway regulation.

publication date

  • February 18, 2000



  • Academic Article



  • eng

PubMed ID

  • 10693759

Additional Document Info

start page

  • 423

end page

  • 34


  • 100


  • 4