title: Muscle contraction is necessary to maintain joint progenitor cell fate.
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 beta-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.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Joy
authors.initials: J
authors.lastname: Kahn
authors.forename: Yulia
authors.initials: Y
authors.lastname: Shwartz
authors.forename: Einat
authors.initials: E
authors.lastname: Blitz
authors.forename: Sharon
authors.initials: S
authors.lastname: Krief
authors.forename: Amnon
authors.initials: A
authors.lastname: Sharir
authors.forename: Dario A
authors.initials: DA
authors.lastname: Breitel
authors.forename: Revital
authors.initials: R
authors.lastname: Rattenbach
authors.forename: Frederic
authors.initials: F
authors.lastname: Relaix
authors.forename: Pascal
authors.initials: P
authors.lastname: Maire
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Rountree
authors.forename: David M
authors.initials: DM
authors.lastname: Kingsley
authors.forename: Elazar
authors.initials: E
authors.lastname: Zelzer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism; D005121:Extremities / Q000196:embryology / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D007596:Joints / Q000166:cytology* / Q000196:embryology*; D051379:Mice; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D018006:Myogenic Regulatory Factors / Q000235:genetics; D038081:Organogenesis; D013234:Stem Cells / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D018006:Myogenic Regulatory Factors; D051176:beta Catenin