PUBLICATION

Twisted gastrulation enhances BMP signaling through chordin dependent and independent mechanisms

Authors
Xie, J., and Fisher, S.
ID
ZDB-PUB-041228-7
Date
2005
Source
Development (Cambridge, England)   132(2): 383-391 (Journal)
Registered Authors
Fisher, Shannon
Keywords
Chordin, Twisted gastrulation, BMP, Dorsoventral patterning, Zebrafish
MeSH Terms
  • Molecular Sequence Data
  • Zebrafish
  • Protein Structure, Tertiary
  • Bone Morphogenetic Proteins/metabolism*
  • Zebrafish Proteins/physiology*
  • Time Factors
  • Gene Expression Regulation
  • Mutagenesis, Site-Directed
  • Phenotype
  • Immunoprecipitation
  • Animals
  • Signal Transduction
  • Green Fluorescent Proteins/metabolism
  • Epitopes/chemistry
  • Intercellular Signaling Peptides and Proteins/chemistry
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Amino Acid Sequence
  • RNA/metabolism
  • Blotting, Western
  • Fishes
  • Glycoproteins/chemistry
  • Glycoproteins/metabolism*
  • Gastrula/metabolism
(all 23)
PubMed
15604098 Full text @ Development
Abstract
BMP signaling is modulated by a number of extracellular proteins, including the inhibitor Chordin, Tolloid-related enzymes (Tld), and the interacting protein Twisted Gastrulation (Tsg). Although in vitro studies have demonstrated Chordin cleavage by Tld enzymes, its significance as a regulatory mechanism in vivo has not been established in vertebrates. In addition, Tsg has been reported in different contexts to either enhance or inhibit BMP signaling through its interactions with Chordin. We have used the zebrafish gastrula to carry out structure/function studies on Chordin, by making versions of Chordin partially or wholly resistant to Tld cleavage and introducing them into chordin-deficient embryos. We examined the cleavage products generated in vivo from wild-type and altered Chordins, and tested their efficacy as BMP inhibitors in the embryo. We demonstrate that Tld cleavage is crucial in restricting Chordin function in vivo, and is carried out by redundant enzymes in the zebrafish gastrula. We also present evidence that partially cleaved Chordin is a stronger BMP inhibitor than the full-length protein, suggesting a positive role for Tld in regulating Chordin. We find that depletion of the embryo for Tsg leads to decreased BMP signaling, and to increased levels of Chordin. Finally, we show that Tsg also enhances BMP signaling in the absence of Chordin, and its depletion can partially rescue the chordin mutant phenotype, demonstrating that important components of the BMP signaling pathway remain unidentified.
Genes / Markers
Figures
Figure Gallery (1 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
tm124a
    		Point Mutation
    tt250
      		Point Mutation
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      twsg1bMO1-twsg1bMRPHLNO
      twsg1bMO3-twsg1bMRPHLNO
      1 - 2 of 2
      Show
      Fish
      Fish
      chrdtt250/tt250
      chrdtt250/tt250 + MO1-twsg1b
      tll1tm124a/tm124a (TU)
      WT
      WT + MO1-twsg1b
      WT + MO3-twsg1b
      1 - 6 of 6
      Show
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      No data available
      Mapping
      No data available
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      Citation
      Xie, J., and Fisher, S. (2005) Twisted gastrulation enhances BMP signaling through chordin dependent and independent mechanisms. Development (Cambridge, England). 132(2):383-391.