Meeting Abstract
The limb is a complex structure comprised of muscle, bone, joints, connective tissues, nerves, and vessels. These tissues, with their distinct embryonic origins and genetic programs, must develop coordinately to maintain functionality as the overall structure is reshaped by natural selection. We focus on a bipedal rodent, the three-toed jerboa, as a model to understand the evolution of development of these integrated tissues. The jerboa has a greatly elongated hindlimb, particularly the metatarsals, and completely lacks intrinsic foot muscles. Flexor muscle loss is associated with expansion of the flexor tendons, presumably to absorb landing forces and to prevent hyperextension across the ankle during ricochetal unguligrade locomotion. Surprisingly, we find that nascent intrinsic foot muscles are present in neonates but most disappear rapidly within the first postnatal week as tendon length and cross-sectional area increases. Electron microscopy and immunohistochemistry reveal sarcomeres progressively disassemble with similarities to a variety of human muscle degenerative diseases. However, while few muscle fibers remain after one week, we do not see apoptotic or necrotic cells during stages of fiber loss. Further, while muscle stem and progenitor cells are present in neonatal feet, they fail to repair and regenerate damaged muscle. We are currently adapting viral lineage tracing methods to permanently mark cells of the muscle lineage. These experiments will allow us to test the hypothesis that muscle loss and tendon expansion are connected by transdetermination of muscle progenitors to a tendon fate, perhaps due to early developmental plasticity.
