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.
Molecular and Cellular Biology Program, Department of Biological Structure, Center for Developmental Biology, University of Washington, Box 357420, Seattle, WA 98195, USA.
Néva P
NP
Meyer
Henk
H
Roelink
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