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Elife. 2019 Oct 15;8. pii: e50645. doi: 10.7554/eLife.50645. [Epub ahead of print]

Evolutionary loss of foot muscle during development with characteristics of atrophy and no evidence of cell death.

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Division of Biological Sciences, Section of Cellular and Developmental Biology, Univeristy of California, San Diego, La Jolla, United States.


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.


developmental biology; evolutionary biology; mouse

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Conflict of interest statement

MT, RT, JE, KC, MF The other authors declare that no competing interests exist. KC Kimberly L Cooper, is on the science advisory board for Synbal, Inc, a company pursuing the use of active genetics technologies in laboratory rodents. This activity is unrelated to the work in this manuscript.

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