Essential and separable roles for Syndecan-3 and Syndecan-4 in skeletal muscle development and regeneration
- D.D.W. Cornelison1,
- Sarah A. Wilcox-Adelman2,
- Paul F. Goetinck2,
- Heikki Rauvala3,
- Alan C. Rapraeger4, and
- Bradley B. Olwin1,5
- 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.
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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1214204.
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↵5 Corresponding author. E-MAIL bradley.olwin@colorado.edu; FAX (303) 492-1587.
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- Accepted July 15, 2004.
- Received April 23, 2004.
- Cold Spring Harbor Laboratory Press
