Abstract
Many species that run or leap across sparsely vegetated habitats, including horses and deer, evolved the severe reduction or complete loss of foot muscles as skeletal elements elongated and digits were lost, and yet the developmental mechanisms remain unknown. Here, we report the natural loss of foot muscles in the bipedal jerboa, Jaculus jaculus. Although adults have no muscles in their feet, newborn animals have muscles that rapidly disappear soon after birth. We were surprised to find no evidence of apoptotic or necrotic cell death during stages of peak myofiber loss, countering well-supported assumptions of developmental tissue remodeling. We instead see hallmarks of muscle atrophy, including an ordered disassembly of the sarcomere associated with upregulation of the E3 ubiquitin ligases, MuRF1 and Atrogin-1. We propose that the natural loss of muscle, which remodeled foot anatomy during evolution and development, involves cellular mechanisms that are typically associated with disease or injury.
Footnotes
We have provided additional evidence in support of an 'atrophy-like' mechanism of muscle cell loss in the form of qRT-PCR data that shows elevated expression of NFkB and Relb, two important upstream regulators of skeletal muscle atrophy through the E3 ubiquitin ligases. We also show a deeper analysis of the functions of muscle progenitor cells and provide evidence that muscle loss may be initiated by non-cell autonomous factor(s).