PUBLICATION

Laminin and Matrix metalloproteinase 11 regulate Fibronectin levels in the zebrafish myotendinous junction

Authors
Jenkins, M.H., Alrowaished, S.S., Goody, M.F., Crawford, B.D., Henry, C.A.
ID
ZDB-PUB-160504-1
Date
2016
Source
Skeletal muscle   6: 18 (Journal)
Registered Authors
Crawford, Bryan D., Henry, Clarissa A.
Keywords
Fibronectin, Laminin, Mmp11, Muscle development, Zebrafish
MeSH Terms
  • Fibronectins/metabolism*
  • Muscle, Skeletal/embryology
  • Muscle, Skeletal/enzymology*
  • Tissue Culture Techniques
  • Muscle Development*
  • Signal Transduction
  • Zebrafish Proteins/metabolism*
  • Time Factors
  • Matrix Metalloproteinase 11/genetics
  • Matrix Metalloproteinase 11/metabolism*
  • Animals, Genetically Modified
  • Mutation
  • Laminin/genetics
  • Laminin/metabolism*
  • Phenotype
  • Zebrafish
  • Tendons/embryology
  • Tendons/enzymology*
  • Animals
  • Down-Regulation
  • Genotype
  • Gene Expression Regulation, Developmental
(all 22)
PubMed
27141287 Full text @ Skelet Muscle
Abstract
Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition.
We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture.
These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mai2TgTransgenic Insertion
    tg210
      Unknown
      ti263a
        Unknown
        wi390TgTransgenic Insertion
        1 - 4 of 4
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        lamc1MO2-lamc1MRPHLNO
        lamc1MO3-lamc1MRPHLNO
        mibp2MO1-mibp2MRPHLNO
        mibp2MO2-mibp2MRPHLNO
        mmp11aMO1-mmp11aMRPHLNO
        mmp11bMO1-mmp11bMRPHLNO
        1 - 6 of 6
        Show
        Fish
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
        Show
        Mapping
        No data available