Muscle Contraction Is Necessary to Maintain Joint Progenitor Cell Fate

Joy Kahn, Yulia Shwartz, Einat Blitz, Sharon Krief, Amnon Sharir, Dario A. Breitel, Revital Rattenbach, Frederic Relaix, Pascal Maire, Ryan B. Rountree, David M. Kingsley, Elazar Zelzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

202 Scopus citations

Abstract

During embryogenesis, organ development is dependent upon maintaining appropriate progenitor cell commitment. Synovial joints develop from a pool of progenitor cells that differentiate into various cell types constituting the mature joint. The involvement of the musculature in joint formation has long been recognized. However, the mechanism by which the musculature regulates joint formation has remained elusive. In this study, we demonstrate, utilizing various murine models devoid of limb musculature or its contraction, that the contracting musculature is fundamental in maintaining joint progenitors committed to their fate, a requirement for correct joint cavitation and morphogenesis. Furthermore, contraction-dependent activation of β-catenin, a key modulator of joint formation, provides a molecular mechanism for this regulation. In conclusion, our findings provide the missing link between progenitor cell fate determination and embryonic movement, two processes shown to be essential for correct organogenesis.

Original languageAmerican English
Pages (from-to)734-743
Number of pages10
JournalDevelopmental Cell
Volume16
Issue number5
DOIs
StatePublished - 19 May 2009

Bibliographical note

Funding Information:
We are grateful to George Kern, Innsbruck, Austria, for the mdg mice and to C. Hartmann, Dr. Y. Yang, M. Pacifici, R. Boot-Handford, and A. Vortkamp for RNA probes. The authors wish to thank C.J. Tabin, J.G. Hall, and R. Schweitzer for suggestions and beneficial discussions, D.J. Glotzer, C. Hartmann, and W. McLean for their helpful reviews of the manuscript, and N. Konstantin for expert editorial assistance. Special thanks to all members of the Zelzer laboratory for advice and suggestions. This work was supported by The Clore Center for Biological Physics, The Leo and Julia Forchheimer Center for Molecular Genetics, The Stanley Chais New Scientist Fund, The Kirk Center for Childhood Cancer and Immunological Disorders, and The David and Fela Shapell Family Center for Genetic Disorders Research. E.Z. is the incumbent of the Martha S. Sagon Career Development Chair.

Keywords

  • DEVBIO

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