Requirement for Scleraxis in the recruitment of mesenchymal progenitors during embryonic tendon elongation

Abstract

The transcription factor scleraxis (<i>Scx</i>) is required for tendon development; however, the function of <i>Scx</i> is not fully understood. Although <i>Scx</i> is expressed by all tendon progenitors and cells, only long tendons are disrupted in the <i>Scx</i>^-/- mutant; short tendons appear normal and the ability of muscle to attach to skeleton is not affected. We recently demonstrated that long tendons are formed in two stages: first, by muscle anchoring to skeleton via a short tendon anlage; and second, by rapid elongation of the tendon in parallel with skeletal growth. Through lineage tracing, we extend these observations to all long tendons and show that tendon elongation is fueled by recruitment of new mesenchymal progenitors. Conditional loss of <i>Scx</i> in mesenchymal progenitors did not affect the first stage of anchoring; however, new cells were not recruited during elongation and long tendon formation was impaired. Interestingly, for tenocyte recruitment, <i>Scx</i> expression was required only in the recruited cells and not in the recruiting tendon. The phenotype of <i>Scx</i> mutants can thus be understood as a failure of tendon cell recruitment during tendon elongation.