The amino-terminal region of Gli3 antagonizes the Shh response and acts in dorsoventral fate specification in the developing spinal cord

• Published in: Developmental biology 2003-05, Vol.257 (2), p.343-355
• Main Authors: Meyer, N.éva P, Roelink, Henk
• Format: Article
• Language: English
• Subjects: Animals; BMP; Body Patterning - physiology; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Chick; Chick Embryo; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryonic Induction - physiology; Eye Proteins; Gene Expression Regulation, Developmental; gli3; Hedgehog Proteins; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Kruppel-Like Transcription Factors; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural; Neural Tube Defects - genetics; Neurons - physiology; Paired Box Transcription Factors; Pallister Hall Syndrome; Patterning; PAX6 Transcription Factor; PAX7 Transcription Factor; Peptide Fragments - genetics; Peptide Fragments - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; shh; Signal Transduction; Spinal cord; Spinal Cord - embryology; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Xenopus Proteins; Zinc Finger Protein Gli3
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/S0012-1606(03)00065-4

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.