Sonic hedgehog differentially regulates expression of GLI and GLI3 during limb development.
Sonic hedgehog is a secreted factor regulating patterning of the anterior-posterior axis in the developing limb. The signaling pathway mediating the transduction of the signal is still poorly understood. In Drosophila several genes are known to act downstream of hedgehog, the fly homolog of Sonic hedgehog. An important gene epistatic to hedgehog is cubitus interruptus, which encodes the fly homolog of a family of vertebrate putative transcription factors, the GLI genes. We have isolated two members of the GLI family from chick, called GLI and GLI3. Their expression patterns in a variety of tissues during embryogenesis suggest that these genes may be targets of the Sonic hedgehog signal. We demonstrate that the two GLI genes are differentially regulated by Sonic hedgehog during limb development. Sonic hedgehog up-regulates GLI transcription, while down-regulating GLI3 expression in the mesenchymal cells of the developing limb bud. Finally, we demonstrate that an activated form of GLI can induce expression of Patched, a known target of Sonic hedgehog, thus implicating GLI as a key transcription factor in the vertebrate hedgehog signaling pathway. In conjunction with evidence from a mouse Gli3 mutant, our data suggest that GLI and GLI3 may have taken two different functions of their Drosophila homolog cubitus interruptus.
Marigo
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V
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Johnson
R L
RL
Vortkamp
A
A
Tabin
C J
CJ
D000818:Animals; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004330:Drosophila; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D018878:Limb Buds / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011506:Proteins; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3