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.
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 funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
© 2021, Abrams et al.
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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.