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 3 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.
Figure 6: Leucine and sucrose induced regeneration in adult mouse digit. (a–b) Amputation was performed on hindpaws of adult (3–6 month old) mice, on digits 2 and 4, proximal to the nail.
(c) Schematic of the distal phalange (P3) and middle phalange (P2). Amputations that remove <30% of P3 (blue line) regenerate, whereas amputations that remove >60% of P3 (red line) do not regenerate. Amputations in the intermediate region can occasionally show partial regenerative response.
(d) Amputations in this study were performed within the red-shaded triangle.
(e) Amputated mice were given regular drinking water (control) or drinking water supplemented with 1.5% L-leucine, 1.5% L-glutamine, and 4–10 w/v% sucrose (2 experiments with 4%, 6 experiments with 10%). Drinking water, control and treated, was refreshed weekly.
(f) A representative paw from the control group. The amputated digits 2 and 4 simply healed the wound and did not regrow the distal phalange.
(g) In this treated mouse, digit 2 (arrow) regrew the distal phalange and nail. Insets on the right show the digit at earlier time points. At week 1, the amputation site still appeared inflamed. At week 3, the beginning of the nail appears (arrow). At week 3, a clear nail plate was observed.
