Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice.
Floor plate cells at the midline of the neural tube are specified by high-level activity of Sonic hedgehog (Shh) secreted by notochord, whereas motor neurons are thought to be specified by a lower level activity of Shh secreted in turn by floor plate cells. In Drosophila, the Gli zinc finger protein Cubitus interruptus functions as a transcription factor activating Hedgehog-responsive genes. We report that the expression of known Shh-responsive genes such as Ptc and Gli1 is downregulated in mutant mice lacking Gli2 function. Gli2 mutants fail to develop a floor plate yet still develop motor neurons, which occupy the ventral midline of the neural tube. Our results imply that Gli2 is required to mediate high level but not low level Shh activity and show that the development of motor neurons can occur in the absence of floor plate induction.
Ding
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Program in Developmental Biology and Division of Endocrinology, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Motoyama
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Gasca
S
S
Mo
R
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Sasaki
H
H
Rossant
J
J
Hui
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CC
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D053823:Hedgehog Proteins; D051542:Hepatocyte Nuclear Factor 3-beta; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins; D009432:Neural Crest / Q000254:growth & development; D009672:Notochord / Q000254:growth & development; D009687:Nuclear Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000032:analysis; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000032:analysis; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
D004268:DNA-Binding Proteins; D005136:Eye Proteins; C496503:Foxa2 protein, mouse; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000605732:Pax6 protein, mouse; D011506:Proteins; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D051542:Hepatocyte Nuclear Factor 3-beta