Fig. 4.

Regulation of cell fate during development of the tendon-bone attachment in the mouse limb. The enthesis is derived from attachment progenitors (APs), which have the potential to form endochondral bone, fibrocartilage and tendon. (A) Tgfβ is necessary to establish APs, which co-express Scx and Sox9. Once established, APs give rise to either Scx⁺ tenocytes, which make tendon, or Sox9⁺ chondrocytes, which make fibrocartilage and bone. Some APs may maintain co-expression of Scx and Sox9, and acquire a hybrid tenochondral phenotype. (B) The APs form as a secondary condensation atop the primary cartilage anlagen at the site of tendon insertion at E12.5. (C) By E13.5, the graded nature of the enthesis begins to emerge; however, it is not known if the intermediate tissue forming at the tendon-bone interface is made from hybrid tenochondral cell type (cells that co-express Scx and Sox9) and/or from discrete cell types (tenocytes and chondrocytes) that intermingle and/or are separated by a cellular boundary. (D) By E14.5-15.5, the graded enthesis has formed, connecting tendon to bone. E, embryonic day.