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

  1. Mai P Tran
  2. Rio Tsutsumi
  3. Joel M Erberich
  4. Kevin D Chen
  5. Michelle D Flores
  6. Kimberly L Cooper  Is a corresponding author
  1. Univeristy of California, San Diego, United States
Research Article
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Cite this article as: eLife 2019;8:e50645 doi: 10.7554/eLife.50645

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.

Article and author information

Author details

  1. Mai P Tran

    Division of Biological Sciences, Section of Cellular and Developmental Biology, Univeristy of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  2. Rio Tsutsumi

    Division of Biological Sciences, Section of Cellular and Developmental Biology, Univeristy of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  3. Joel M Erberich

    Division of Biological Sciences, Section of Cellular and Developmental Biology, Univeristy of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  4. Kevin D Chen

    Division of Biological Sciences, Section of Cellular and Developmental Biology, Univeristy of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  5. Michelle D Flores

    Division of Biological Sciences, Section of Cellular and Developmental Biology, Univeristy of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  6. Kimberly L Cooper

    Division of Biological Sciences, Section of Cellular and Developmental Biology, Univeristy of California, San Diego, La Jolla, United States
    For correspondence
    kcooper@ucsd.edu
    Competing interests
    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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5892-8838

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.

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.

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Publication history

  1. Received: July 28, 2019
  2. Accepted: October 1, 2019
  3. Accepted Manuscript published: October 15, 2019 (version 1)
  4. 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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