The amino-terminal region of Gli3 antagonizes the Shh response and acts in dorsoventral fate specification in the developing spinal cord.
A concentration gradient of Shh is thought to pattern the ventral neural tube, and these ventral cell types are absent in shh-/- mice. Based on in vitro and genetic studies, the zinc finger-containing transcription factors Gli 1, 2, and 3 are mediators of the Shh intracellular response. The floorplate and adjacent cell types are absent in gli1-/-;gli2-/- mice, but part of the Shh-/- phenotype in the neural tube is alleviated in the Shh-/-;gli3-/- double mutant. This is consistent with the predicted role of Gli3 as a repressor of the Shh response. Gli3 repressor activity is blocked by Shh. In order to test the role of the repressor form of Gli3 in the neural tube, a truncated version of Gli3 (Gli3R*) was designed to mimic a Pallister Hall allele. Gli3R* acts as a constitutive repressor independent of Shh signaling. Misexpression of Gli3R* in the chick neural tube caused a ventral expansion of class-I, dorsal progenitor proteins and a loss of class-II, ventral progenitor proteins consistent with expected activity as a repressor of the Shh response. Activation of the BMP response is sufficient to maintain gli3 expression in neural plate explants, which might be a mechanism by which BMPs antagonize the Shh response.
Meyer
Néva P
NP
Molecular and Cellular Biology Program, Department of Biological Structure, Center for Developmental Biology, University of Washington, Box 357420, Seattle, WA 98195, USA.
Roelink
Henk
H
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004627:Embryonic Induction / Q000502:physiology*; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009436:Neural Tube Defects / Q000235:genetics; D009474:Neurons / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000074290:Zinc Finger Protein Gli3
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C491328:Nkx6-1 protein, mouse; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D010446:Peptide Fragments; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000074290:Zinc Finger Protein Gli3; C525812:bmp4 protein, Xenopus