Control of tendon cell fate in the embryonic limb: A molecular perspective.

The molecular cascade underlying tendon formation starts when progenitor cells begin to express the Scleraxis (Scx) gene. Scx knockout mice develop some but not all tendons, suggesting that additional factors are necessary for tendon commitment, maintenance, and differentiation. Other transcription factors, such as Mohawk (Mkx) or early growth response (Egr), maintain Scx expression and extracellular matrix formation during fibrillogenesis. The inhibition of wingless and int-related protein signaling is necessary and sufficient to induce the expression of Scx. Once the commitment of tenogenic lineage occurs, transforming growth factor-beta (TGFβ) induces the Scx gene expression, becoming involved in the maintenance of tendon cell fate. From this point of view, we discussed two phases of the tenogenic process during limb development: dependent and independent of mechanical forces. Finally, we highlight the importance of understanding embryonic tendon development to improve therapeutic strategies in regenerative medicines for tendons. [ABSTRACT FROM AUTHOR]