Bone Ridge Patterning during Musculoskeletal Assembly Is Mediated through SCX Regulation of Bmp4 at the Tendon-Skeleton Junction

被引:232
作者
Blitz, Einat [1 ]
Viukov, Sergey [1 ]
Sharir, Amnon [1 ,2 ]
Shwartz, Yulia [1 ]
Galloway, Jenna L. [3 ]
Pryce, Brian A. [4 ]
Johnson, Randy L. [5 ]
Tabin, Clifford J. [3 ]
Schweitzer, Ronen [4 ]
Zelzer, Elazar [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
[2] Hebrew Univ Jerusalem, Fac Agr Food & Environm Qual Sci, Koret Sch Vet Med, IL-76100 Rehovot, Israel
[3] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[4] Shriners Hosp Children, Div Res, Portland, OR 97239 USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA
基金
以色列科学基金会;
关键词
MUTATION MUSCULAR DYSGENESIS; TRANSPLANTED LIMB PRIMORDIA; DEVELOPMENTAL GENETICS; TRANSCRIPTION FACTORS; EMBRYONIC CHICK; GROWTH-PLATE; II RECEPTOR; LONG BONES; MUSCLE; SCLERAXIS;
D O I
10.1016/j.devcel.2009.10.010
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
引用
收藏
页码:861 / 873
页数:13
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