Muscle contraction is necessary to maintain joint progenitor cell fate.
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.
Kahn
Joy
J
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Shwartz
Yulia
Y
Blitz
Einat
E
Krief
Sharon
S
Sharir
Amnon
A
Breitel
Dario A
DA
Rattenbach
Revital
R
Relaix
Frederic
F
Maire
Pascal
P
Rountree
Ryan B
RB
Kingsley
David M
DM
Zelzer
Elazar
E
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
D018398:Homeodomain Proteins; D018006:Myogenic Regulatory Factors; D051176:beta Catenin