Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Basic Helix-Loop-Helix Transcription Factors
-
Cell Death
-
Cytokines
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / physiology*
-
Extremities / embryology*
-
Fibroblast Growth Factors / genetics
-
Fibroblast Growth Factors / metabolism
-
Gene Expression Regulation, Developmental
-
Genes, Homeobox
-
Hedgehog Proteins
-
Homeodomain Proteins / genetics
-
Homeodomain Proteins / metabolism
-
Intercellular Signaling Peptides and Proteins*
-
Kruppel-Like Transcription Factors
-
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
-
Patched Receptors
-
Polydactyly / genetics
-
Proteins / genetics
-
Proteins / physiology
-
Receptors, Cell Surface
-
Signal Transduction
-
Trans-Activators / genetics
-
Trans-Activators / physiology*
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
-
Transcription Factors / physiology*
-
Zebrafish Proteins
-
Zinc Finger Protein GLI1
-
Zinc Finger Protein Gli3
Substances
-
ALX4 protein, human
-
Basic Helix-Loop-Helix Transcription Factors
-
Cktsf1b1 protein, mouse
-
Cytokines
-
DNA-Binding Proteins
-
GREM1 protein, human
-
Gli3 protein, mouse
-
Hand2 protein, mouse
-
Hedgehog Proteins
-
Homeodomain Proteins
-
Intercellular Signaling Peptides and Proteins
-
Kruppel-Like Transcription Factors
-
Membrane Proteins
-
Nerve Tissue Proteins
-
Oncogene Proteins
-
Patched Receptors
-
Proteins
-
Receptors, Cell Surface
-
Shh protein, mouse
-
Trans-Activators
-
Transcription Factors
-
Zebrafish Proteins
-
Zinc Finger Protein GLI1
-
Zinc Finger Protein Gli3
-
fibroblast growth factor 14
-
hand2 protein, zebrafish
-
Fibroblast Growth Factors