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

Overview

MeSH

  • Animals
  • Antibodies
  • Base Sequence
  • Body Patterning
  • COS Cells
  • Chick Embryo
  • Cyclic AMP-Dependent Protein Kinases
  • DNA, Complementary
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Humans
  • Kruppel-Like Transcription Factors
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phosphorylation
  • Transcription, Genetic

MeSH Major

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

abstract

  • 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

has subject area

  • Animals
  • Antibodies
  • Base Sequence
  • Body Patterning
  • COS Cells
  • Chick Embryo
  • Cyclic AMP-Dependent Protein Kinases
  • DNA, Complementary
  • DNA-Binding Proteins
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Humans
  • Kruppel-Like Transcription Factors
  • Limb Buds
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Xenopus Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 10693759

Additional Document Info

start page

  • 423

end page

  • 434

volume

  • 100

number

  • 4