Journal
DEVELOPMENTAL CELL
Volume 17, Issue 6, Pages 861-873Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2009.10.010
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Funding
- Israel Science Foundation [499/05]
- Minerva [M941]
- The Leo and Julia Forchheimer Center for Molecular Genetics
- The Stanley Chats New Scientist Fund
- The Kirk Center for Childhood Cancer and Immunological Disorders
- The David and Fela Shapell Family Center for Genetic Disorders Research
- The Clore Center for Biological Physics, Benozyo Institute
- NIH [PO1 DK56246]
- NICHID [F32HD057701]
- NIAMS [R01 AR055640]
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During the assembly of the musculoskeletal system, bone ridges provide a stable anchoring point and stress dissipation for the attachment of muscles via tendons to the skeleton. In this study, we investigate the development of the deltoid tuberosity as a model for bone ridge formation. We show that the deltoid tuberosity develops through endochondral ossification in a two-phase process: initiation is regulated by a signal from the tendons, whereas the subsequent growth phase is muscle dependent. We then show that the transcription factor scleraxis (SCX) regulates Bmp4 in tendon cells at their insertion site. The inhibition of deltoid tuberosity formation and several other bone ridges in embryos in which Bmp4 expression was blocked specifically in Scx-expressing cells implicates BMP4 as a key mediator of tendon effects on bone ridge formation. This study establishes a mechanistic basis for tendon-skeleton regulatory interactions during musculoskeletal assembly and bone secondary patterning.
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