PUBLICATION

Mechanical force regulates tendon extracellular matrix organization and tenocyte morphogenesis through TGFbeta signaling

Authors
Subramanian, A., Kanzaki, L.F., Galloway, J.L., Schilling, T.F.
ID
ZDB-PUB-181127-80
Date
2018
Source
eLIFE   7: (Journal)
Registered Authors
Galloway, Jenna, Schilling, Tom, Subramanian, Arul
Keywords
cell biology, developmental biology, zebrafish
MeSH Terms
  • Morphogenesis*
  • Animals, Genetically Modified
  • Luminescent Proteins/analysis
  • Luminescent Proteins/genetics
  • Zebrafish
  • Transforming Growth Factor beta/metabolism*
  • Genes, Reporter
  • Cell Shape
  • Tenocytes/cytology*
  • Tenocytes/physiology
  • Tendons/physiology*
  • Extracellular Matrix/metabolism*
  • Recombinant Fusion Proteins/analysis
  • Recombinant Fusion Proteins/genetics
  • Stress, Mechanical*
  • Animals
  • Signal Transduction*
(all 17)
PubMed
30475205 Full text @ Elife
Abstract
Mechanical forces between cells and extracellular matrix (ECM) influence cell shape and function. Tendons are ECM-rich tissues connecting muscles with bones that bear extreme tensional force. Analysis of transgenic zebrafish expressing mCherry driven by the tendon determinant scleraxis reveals that tendon fibroblasts (tenocytes) extend arrays of microtubule-rich projections at the onset of muscle contraction. In the trunk, these form a dense curtain along the myotendinous junctions at somite boundaries, perpendicular to myofibers, suggesting a role as force sensors to control ECM production and tendon strength. Paralysis or destabilization of microtubules reduces projection length and surrounding ECM, both of which are rescued by muscle stimulation. Paralysis also reduces SMAD3 phosphorylation in tenocytes and chemical inhibition of TGFβ signaling shortens tenocyte projections. These results suggest that TGFβ, released in response to force, acts on tenocytes to alter their morphology and ECM production, revealing a feedback mechanism by which tendons adapt to tension.
Genes / Markers
Figures
Figure Gallery (6 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fb301TgTransgenic Insertion
    ir1092
      Unknown
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      1 - 2 of 2
      Show
      Antibodies
      Name Type Antigen Genes Isotypes Host Organism
      Ab1-thbs4bpolyclonalRabbit
      Ab3-smad3polyclonal
        IgGRabbit
        Ab4-lampolyclonal
          IgGRabbit
          Ab5-fnpolyclonal
            IgGRabbit
            Ab-A4.1025monoclonal
              IgG2aMouse
              1 - 5 of 5
              Show
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              mCherryEFGmCherry
              1 - 1 of 1
              Show
              Mapping
              No data available