title: Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Einat
authors.initials: E
authors.lastname: Blitz
authors.forename: Sergey
authors.initials: S
authors.lastname: Viukov
authors.forename: Amnon
authors.initials: A
authors.lastname: Sharir
authors.forename: Yulia
authors.initials: Y
authors.lastname: Shwartz
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Galloway
authors.forename: Brian A
authors.initials: BA
authors.lastname: Pryce
authors.forename: Randy L
authors.initials: RL
authors.lastname: Johnson
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Tabin
authors.forename: Ronen
authors.initials: R
authors.lastname: Schweitzer
authors.forename: Elazar
authors.initials: E
authors.lastname: Zelzer
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D010012:Osteogenesis; D013710:Tendons / Q000196:embryology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; C525810:Bmp4 protein, mouse; C503815:Scx protein, mouse