Tendon-bone attachment unit is formed modularly by a distinct pool of Scx-and Sox9-positive progenitors

Einat Blitz, Amnon Sharir, Haruhiko Akiyama, Elazar Zelzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

Abstract

The assembly of the musculoskeletal system requires the formation of an attachment unit between a bone and a tendon. Tendons are often inserted into bone eminences, superstructures that improve the mechanical resilience of the attachment of muscles to the skeleton and facilitate movement. Despite their functional importance, little is known about the development of bone eminences and attachment units. Here, we show that bone eminence cells are descendants of a unique set of progenitors and that superstructures are added onto the developing long bone in a modular fashion. First, we show that bone eminences emerge only after the primary cartilage rudiments have formed. Cell lineage analyses revealed that eminence cells are not descendants of chondrocytes. Moreover, eminence progenitors were specified separately and after chondroprogenitors of the primary cartilage. Fields of Sox9-positive, Scxpositive, Col2a1-negative cells identified at presumable eminence sites confirm the identity and specificity of these progenitors. The loss of eminences in limbs in which Sox9 expression was blocked in Scx-positive cells supports the hypothesis that a distinct pool of Sox9-and Scx-positive progenitors forms these superstructures. We demonstrate that TGFβ signaling is necessary for the specification of bone eminence progenitors, whereas the SCX/BMP4 pathway is required for the differentiation of these progenitors to eminenceforming cells. Our findings suggest a modular model for bone development, involving a distinct pool of Sox9-and Scx-positive progenitor cells that form bone eminences under regulation of TGFβ and BMP4 signaling. This model offers a new perspective on bone morphogenesis and on attachment unit development during musculoskeletal assembly.

Original languageAmerican English
Pages (from-to)2680-2690
Number of pages11
JournalDevelopment (Cambridge)
Volume140
Issue number13
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Attachment unit
  • BMP4
  • Cartilage
  • Modularity
  • Mouse
  • Musculoskeletal system
  • Patterning
  • Progenitors
  • SCX
  • SOX9
  • Skeleton
  • Specification
  • TGFβ
  • Tendons

Fingerprint

Dive into the research topics of 'Tendon-bone attachment unit is formed modularly by a distinct pool of Scx-and Sox9-positive progenitors'. Together they form a unique fingerprint.

Cite this