A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice

  1. Michael J Abrams
  2. Fayth Hui Tan
  3. Yutian Li
  4. Ty Basinger
  5. Martin L Heithe
  6. Anish Sarma
  7. Iris T Lee
  8. Zevin J Condiotte
  9. Misha Raffiee
  10. John O Dabiri
  11. David A Gold
  12. Lea Goentoro  Is a corresponding author
  1. University of California, Berkeley, United States
  2. California Institute of Technology, United States
  3. Bloomsburg University, United States
  4. Stanford University, United States
  5. University of California, Davis, United States

Abstract

Can limb regeneration be induced? Few have pursued this question, and an evolutionarily conserved strategy has yet to emerge. This study reports a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish Aurelia was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adult Drosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files, as well as deposited to the open repository CaltechDATA.

The following data sets were generated

Article and author information

Author details

  1. Michael J Abrams

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States
    Competing interests
    Michael J Abrams, Inventor in patent rights application for findings in the manuscript..
  2. Fayth Hui Tan

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    Fayth Hui Tan, Inventor in patent rights application for findings in the manuscript..
  3. Yutian Li

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  4. Ty Basinger

    Department of Biology and Allied Health Sciences, Bloomsburg University, Bloomsburg, United States
    Competing interests
    Ty Basinger, Inventor in patent rights application for findings in the manuscript..
  5. Martin L Heithe

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    Martin L Heithe, Inventor in patent rights application for findings in the manuscript..
  6. Anish Sarma

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  7. Iris T Lee

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  8. Zevin J Condiotte

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  9. Misha Raffiee

    Department of Bioengineering, Stanford University, Paolo Alto, United States
    Competing interests
    No competing interests declared.
  10. John O Dabiri

    Graduate Aerospace Laboratories and Mechanical Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  11. David A Gold

    Department of Earth and Planetary Sciences, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  12. Lea Goentoro

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    goentoro@caltech.edu
    Competing interests
    Lea Goentoro, Inventor in patent rights application for findings in the manuscript..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3904-0195

Funding

James S. McDonnell Foundation (Complex Systems Science,220020365)

  • Lea Goentoro

National Science Foundation (Graduate Research Fellowship,1144469)

  • Michael J Abrams

James E. and Charlotte Fedde Cordes (Postdoctoral Fellowship)

  • David A Gold

Center for Environmental Microbial Interactions

  • Zevin J Condiotte
  • David A Gold
  • Lea Goentoro

Charles Trimble and Caltech's Biology and Biological Chair's Council Inducing Regeneration Fund

  • Lea Goentoro

Center of Evolutionary Sciences at Caltech

  • Yutian Li
  • Lea Goentoro

Summer Undergraduate Research Fellowship

  • Iris T Lee
  • Lea Goentoro

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Virginie Courtier-Orgogozo, Université Paris-Diderot CNRS, France

Ethics

Animal experimentation: All studies comply with relevant ethical regulations for animal testing and research, and received ethical approval by the Institutional Animal Care and Use Committees (IACUC) at the California Institute of Technology. The protocol was approved by the IACUC at Caltech under the protocol number 1773-19 . All mouse surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Version history

  1. Preprint posted: November 22, 2020 (view preprint)
  2. Received: November 22, 2020
  3. Accepted: November 22, 2021
  4. Accepted Manuscript published: December 7, 2021 (version 1)
  5. Version of Record published: January 21, 2022 (version 2)
  6. Version of Record updated: February 9, 2022 (version 3)
  7. Version of Record updated: June 22, 2023 (version 4)

Copyright

© 2021, Abrams 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.

Metrics

  • 11,284
    views
  • 837
    downloads
  • 12
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Michael J Abrams
  2. Fayth Hui Tan
  3. Yutian Li
  4. Ty Basinger
  5. Martin L Heithe
  6. Anish Sarma
  7. Iris T Lee
  8. Zevin J Condiotte
  9. Misha Raffiee
  10. John O Dabiri
  11. David A Gold
  12. Lea Goentoro
(2021)
A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice
eLife 10:e65092.
https://doi.org/10.7554/eLife.65092

Share this article

https://doi.org/10.7554/eLife.65092

Further reading

    1. Evolutionary Biology
    2. Stem Cells and Regenerative Medicine
    Yutian Li, Anish A Sarma ... Lea Goentoro

    Previously we reported evidence that a regenerative response in the appendages of moon jellyfish, fruit flies, and mice can be promoted by nutrient modulation (Abrams et al., 2021). Sustar and Tuthill subsequently reported that they had not been able to reproduce the induced regenerative response in flies (Sustar and Tuthill, 2023). Here we discuss that differences in the amputation method, treatment concentrations, age of the animals, and stress management explain why they did not observe a regenerative response in flies. Typically, 30–50% of treated flies showed response in our assay.