PUBLICATION

Zebrafish furin mutants reveal intricacies in regulating Endothelin1 signaling in craniofacial patterning

Authors
Walker, M.B., Miller, C.T., Talbot, J.C., Stock, D.W., and Kimmel, C.B.
ID
ZDB-PUB-060517-6
Date
2006
Source
Developmental Biology   295(1): 194-205 (Journal)
Registered Authors
Kimmel, Charles B., Miller, Craig T., Stock, David W., Talbot, Jared, Walker, Macie B.
Keywords
none
MeSH Terms
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Furin/genetics
  • Furin/metabolism*
  • Amino Acid Sequence
  • HMGB Proteins/genetics
  • HMGB Proteins/metabolism
  • SOX9 Transcription Factor
  • Gene Expression Regulation, Developmental
  • Body Patterning/physiology*
  • Signal Transduction
  • Male
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Head/embryology
  • Animals
  • Mutation
  • Molecular Sequence Data
  • Endothelin-1/genetics
  • Endothelin-1/metabolism*
  • Gene Duplication
  • Chromosome Mapping
  • Embryo, Nonmammalian/metabolism
  • Extremities/embryology
  • Female
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
(all 31)
PubMed
16678149 Full text @ Dev. Biol.
Abstract
Endothelin1 (Edn1) signaling promotes ventral character to the facial skeleton. In zebrafish edn1 mutants, the ventral jaw structures are severely reduced and fused to their dorsal counterparts, with a loss of joints that normally form at an intermediate dorsal-ventral position. Loss of function at another locus, sturgeon, also yields joint losses, but only mild reductions in the ventral jaw structures. We show that sturgeon encodes one of two orthologs of Furin present in zebrafish, and that both furin genes may function partially redundantly to activate Edn1 signaling. Supporting this hypothesis, early expression of edn1-dependent genes is downregulated in sturgeon (furinA) mutants. Later in development, expression of most of these genes recovers to near wild-type levels in furinA mutants but not in edn1 mutants. The recovery explains the less severe furinA mutant skeletal phenotype and suggests that late gene expression is dependent on a critical level of Edn1 signaling not present in the more severe edn1 mutants. However, expression defects in the intermediate joint-forming domains in both mutants persist, explaining the joint losses observed later in both mutants. We further show that in both mutants the arches fail to correctly undergo ventral elongation before skeletogenesis begins and propose a model in which this failure is largely responsible for the loss of an Edn1-dependent compartmentation of the arch into the intermediate and ventral domains.
Genes / Markers
Figures
Figure Gallery (15 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b963
    Point Mutation
    furina_unspecified
      Unspecified
      td204e
        Point Mutation
        tf216b
          Point Mutation
          tg419
            Point Mutation
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            dlx3bMO1-dlx3bMRPHLNO
            dlx5aMO1-dlx5aMRPHLNO
            edn1MO1-edn1MRPHLNO
            furinaMO1-furinaMRPHLNO
            furinbMO1-furinbMRPHLNO
            1 - 5 of 5
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            Fish
            Antibodies
            No data available
            Orthology
            No data available
            Engineered Foreign Genes
            No data available
            Mapping
            Entity Type Entity Symbol Location
            Featuretd204eChr: 7 Details
            Featuretg419Chr: 7 Details
            GENEfurinbChr: 25 Details
            SSLPz1206Chr: 7 Details
            SSLPz20963Chr: 7 Details
            1 - 5 of 5
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