A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice
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.
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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.
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.
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.
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Further reading
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- Evolutionary Biology
- Stem Cells and Regenerative Medicine
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.