Evolutionary loss of foot muscle during development with characteristics of atrophy and no evidence of cell death
- Univeristy of California, San Diego, United States
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.
Data availability
All raw images and other associated data for this manuscript, including TEM, immunofluorescence, and qRT-PCR, have been curated and deposited with Zenodo. They can be found at the object identifier https://doi.org/10.5281/zenodo.3404257.
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Evolutionary loss of foot muscle during development with characteristics of atrophy and no evidence of cell deathZenodo, https://doi.org/10.5281/zenodo.3404257.
Article and author information
Author details
Funding
Pew Charitable Trusts (Pew Biomedical Scholarship)
- Kimberly L Cooper
Kinship Foundation (Searle Scholarship)
- Kimberly L Cooper
David and Lucile Packard Foundation (Packard Fellowships in Science and Engineering)
- Kimberly L Cooper
National Institutes of Health (R21 AR074609-01A1)
- Kimberly L Cooper
National Institutes of Health (T32GM724039)
- Mai P Tran
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#S13246 and S14014) of the University of California San Diego. Oversight of research using jerboas is also provided by the US Department of Agriculture (USDA). Every effort was made to minimize suffering.
Version history
- Received: July 28, 2019
- Accepted: October 1, 2019
- Accepted Manuscript published: October 15, 2019 (version 1)
- Version of Record published: November 14, 2019 (version 2)
Copyright
© 2019, Tran et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Evolutionary loss of foot muscle during development with characteristics of atrophy and no evidence of cell death
eLife 8:e50645.
https://doi.org/10.7554/eLife.50645
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