Essential and separable roles for Syndecan-3 and Syndecan-4 in skeletal muscle development and regeneration

  1. D.D.W. Cornelison1,
  2. Sarah A. Wilcox-Adelman2,
  3. Paul F. Goetinck2,
  4. Heikki Rauvala3,
  5. Alan C. Rapraeger4, and
  6. Bradley B. Olwin1,5
  1. 1Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA; 2Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA; 3Neuroscience Center, Department of Biosciences, and Institute of Biotechnology, University of Helsinki, Helsinki FIN-00014, Finland; 4Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA

Abstract

Syndecan-3 and syndecan-4 function as coreceptors for tyrosine kinases and in cell adhesion. Syndecan-3-/- mice exhibit a novel form of muscular dystrophy characterized by impaired locomotion, fibrosis, and hyperplasia of myonuclei and satellite cells. Explanted syndecan-3-/- satellite cells mislocalize MyoD, differentiate aberrantly, and exhibit a general increase in overall tyrosine phosphorylation. Following induced regeneration, the hyperplastic phenotype is recapitulated. While there are fewer apparent defects in syndecan-4-/- muscle, explanted satellite cells are deficient in activation, proliferation, MyoD expression, myotube fusion, and differentiation. Further, syndecan-4-/- satellite cells fail to reconstitute damaged muscle, suggesting a unique requirement for syndecan-4 in satellite cell function.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1214204.

  • 5 Corresponding author. E-MAIL bradley.olwin{at}colorado.edu; FAX (303) 492-1587.

    • Accepted July 15, 2004.
    • Received April 23, 2004.
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