Journal Article

Progression of Vertebrate Limb Development through SHH-Mediated Counteraction of GLI3

Drenth, Thijs, Goedemans, Hans J., Zeller, Rolf, Welscher, Pascal te, Meijlink, Frits, Zuniga, Aimée, Kuijper, Sanne

2002

Overview

Distal limb development and specification of digit identities in tetrapods are under the control of a mesenchymal organizer called the polarizing region. Sonic Hedgehog (SHH) is the morphogenetic signal produced by the polarizing region in the posterior limb bud. Ectopic anterior SHH signaling induces digit duplications and has been suspected as a major cause underlying congenital malformations that result in digit polydactyly. Here, we report that the polydactyly of Gli3-deficient mice arises independently of SHH signaling. Disruption of one or both Gli3 alleles in mouse embryos lacking Shh progressively restores limb distal development and digit formation. Our genetic analysis indicates that SHH signaling counteracts GLI3-mediated repression of key regulator genes, cell survival, and distal progression of limb bud development.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science,American Association for the Advancement of Science (AAAS)
• Subject: Alleles / Animal embryo / Animals / Apoptosis / Basic Helix-Loop-Helix Transcription Factors / Biological and medical sciences / Biology / Cell Death / Cellular Biology / Congenital defects / Control loops / DNA-Binding Proteins - genetics / DNA-Binding Proteins - physiology / Embryological research / Embryology, Experimental / Embryology: invertebrates and vertebrates. Teratology / Embryos / Extremities - embryology / Feedback (Response) / Fibroblast Growth Factors - genetics / Fibroblast Growth Factors - metabolism / Fundamental and applied biological sciences. Psychology / Gene Expression Regulation, Developmental / Genes / Genes, Homeobox / Genetics / Genotypes / Hedgehog Proteins / Homeodomain Proteins - genetics / Homeodomain Proteins - metabolism / Intercellular Signaling Peptides and Proteins / Kruppel-Like Transcription Factors / Life Sciences / Limb buds / Limb Buds - cytology / Limb Buds - embryology / Limb Buds - metabolism / Membrane Proteins - genetics / Membrane Proteins - metabolism / Mice / Mutation / Nerve Tissue Proteins / Oncogene Proteins - genetics / Oncogene Proteins - metabolism / Organogenesis. Fetal development / Organogenesis. Physiological fonctions / Patched Receptors / Phenotypes / Polydactyly / Polydactyly - genetics / Proteins - genetics / Proteins - physiology / Receptors, Cell Surface / Rodents / Signal Transduction / Trans-Activators - genetics / Trans-Activators - physiology / Transcription Factors - genetics / Transcription Factors - metabolism / Transcription Factors - physiology / Transcripts (Written Records) / Vertebrates / Zebrafish Proteins / Zinc Finger Protein GLI1 / Zinc Finger Protein Gli3