The Shh-independent activator function of the full-length Gli3 protein and its role in vertebrate limb digit patterning
| Autor: | Baolin Wang, Ulrich Rüther, Chengbing Wang |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
musculoskeletal diseases
animal structures Body Patterning Kruppel-Like Transcription Factors Repressor Gli3 activator Mice Transgenic Nerve Tissue Proteins Article Mice Zinc Finger Protein Gli3 GLI3 Animals Humans Hedgehog Proteins Sonic hedgehog Hedgehog Molecular Biology Regulation of gene expression biology Activator (genetics) Gli3 repressor fungi Wild type Gene Expression Regulation Developmental Extremities Cell Biology Molecular biology Mice Mutant Strains body regions Mice Inbred C57BL Repressor Proteins Phenotype embryonic structures biology.protein Trans-Activators Limb patterning Developmental Biology |
| Zdroj: | Developmental Biology. 305(2):460-469 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2007.02.029 |
| Popis: | Anterior–posterior (A/P) limb patterning in vertebrates is determined by the counteraction between the Sonic Hedgehog (Shh) and the Gli3 transcription factor. Shh exerts its effect on Gli3 by regulating the full-length Gli3 protein processing to generate a Gli3 repressor gradient along the A/P axis of the limb. However, it is not clear whether the full-length Gli3 is an activator in vivo and plays any role in the limb patterning. Here we show that mouse limbs expressing only a Gli3 repressor form exhibit mild polysyndactyly and a partial loss of digit identity, while limbs expressing only a full-length Gli3 protein display severe polysyndactyly and a complete loss of digit identity. Interestingly, when the full-length Gli3 and the repressor are equally expressed in the limb, the digit patterning is overall normal except for an extra anterior digit. Furthermore, in the presence of one Gli3 wild type allele, a Gli3 mutant allele that expresses only the full-length form can rescue the Shh mutant digit phenotype to a great extent. The full-length Gli3 protein can also activate Shh target gene expression without Shh. Thus, our data indicate that the full-length Gli3 protein is an activator in vivo and that the ratio of the Gli3 activator to repressor, but neither the Gli3 repressor gradient nor the Gli3 activator/repressor ratio gradient, determines limb digit patterning. |
| Databáze: | OpenAIRE |
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