Molecular regulation of tendon cell fate during development

Although there have been several advances identifying novel mediators of tendon induction, differentiation, and patterning, much of the basic landscape of tendon biology from developmental stages onward remain almost completely undefined. During the New Frontiers in Tendon Research meeting, a group of developmental biologists with expertise across musculoskeletal disciplines identified key challenges for the tendon development field. The tools generated and the molecular regulators identified in developmental research have enhanced mechanistic studies in tendon injury and repair, both by defining benchmarks for success, as well as informing regenerative strategies. To address the needs of the orthopedic research community, this review will therefore focus on three key areas in tendon development that may have critical implications for the fields of tendon repair/regeneration and tendon tissue engineering, including functional markers of tendon cell identity, signaling regulators of tendon induction and differentiation, and in vitro culture models for tendon cell differentiation. Our goal is to provide a useful list of the currently known molecular players and their function in tendon differentiation within the context of development.