Mouse limbs expressing only the Gli3 repressor resemble those of Sonic hedgehog mutants. Academic Article uri icon

Overview

MeSH

  • Animals
  • Base Sequence
  • DNA Primers
  • Immunoblotting
  • In Situ Hybridization
  • Integrases
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutagenesis

MeSH Major

  • Body Patterning
  • Extremities
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Phenotype

abstract

  • Anterioposterior vertebrate limb patterning is controlled by opposing action between Sonic Hedgehog (Shh) and the Gli3 transcriptional repressor. Unexpectedly, Gli3(Δ699) mutant mice, which are thought to express only a Gli3 repressor and not the full-length activator, exhibit limb phenotypes inconsistent with those of Shh mutant mice. Therefore, it remains debatable whether Shh patterns the anterioposterior limb primarily by inhibiting generation of the Gli3 repressor. However, one caveat is that Gli3(Δ699) may not be as potent as the natural form of Gli3 repressor because of the nature of the mutant allele. In the present study, we created a conditional Gli3 mutant allele that exclusively expresses Gli3 repressor in the presence of Cre recombinase. Using this mutant, we show that the phenotypes of mouse limbs expressing only the Gli3 repressor exhibit no or single digit, resembling those of Shh mutant limbs. Consistent with the limb phenotypes, the expression of genes dependent on Shh signaling is also inhibited in both mutants. This inhibition by the Gli3 repressor is independent of Shh. Thus, our study clarifies the current controversy and provides important genetic evidence to support the hypothesis that Shh patterns the anterioposterior limb primarily through the inhibition of Gli3 repressor formation. Copyright © 2013 Elsevier Inc. All rights reserved.

publication date

  • July 15, 2013

has subject area

  • Animals
  • Base Sequence
  • Body Patterning
  • DNA Primers
  • Extremities
  • Hedgehog Proteins
  • Immunoblotting
  • In Situ Hybridization
  • Integrases
  • Kruppel-Like Transcription Factors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutagenesis
  • Nerve Tissue Proteins
  • Phenotype

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3707282

Digital Object Identifier (DOI)

  • 10.1016/j.ydbio.2013.04.025

PubMed ID

  • 23644062

Additional Document Info

start page

  • 221

end page

  • 228

volume

  • 379

number

  • 2