Mechanobiology of Tendon Development
While it is appreciated that tendons sense and respond to mechanical forces, the mechanisms by which tendons translate forces into biological outputs are almost completely unknown. In the mouse embryo, we previously found that tendon progenitors are induced and differentiate in muscle paralysis mutants, however lateral growth is subsequently compromised and tendons are qualitatively thinner and mis-patterned in later stages, indicating a role for muscle contractile forces in tendon growth. Although these studies establish a role for muscle loading in embryonic tendon development, the requirement for muscle loading during postnatal tendon growth and maturation is unclear. To address these questions, we combine genetic and botulinum toxin induced mouse models of muscle paralysis with in vitro bioreactor loading of engineered tendons to study tendon mechanobiology. One major focus is identifying the mechanotransduction pathways that regulate embryonic and postnatal tendon development.