Aztekin C and Storer MA (2022), To regenerate or not to regenerate: Vertebrate ...

XB-ART-58961

Wound Repair Regen 2022 Nov 01;306:623-635. doi: 10.1111/wrr.13000.

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To regenerate or not to regenerate: Vertebrate model organisms of regeneration-competency and -incompetency.

Aztekin C , Storer MA .

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Why only certain species can regenerate their appendages (e.g. tails and limbs) remains one of the biggest mysteries of nature. Unlike anuran tadpoles and salamanders, humans and other mammals cannot regenerate their limbs, but can only regrow lost digit tips under specific circumstances. Numerous hypotheses have been postulated to explain regeneration-incompetency in mammals. By studying model organisms that show varying regenerative abilities, we now have more opportunities to uncover what contributes to regeneration-incompetency and functionally test which perturbations restore appendage regrowth. Particularly, Xenopus laevis tail and limb, and mouse digit tip model systems exhibit naturally occurring variations in regenerative capacities. Here, we discuss major hypotheses that are suggested to contribute to regeneration-incompetency, and how species with varying regenerative abilities reflect on these hypotheses.

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Species referenced: Xenopus laevis

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Figure 1. Selected model organisms of regeneration-competency and regenerationincompetency. (A) (Top) Xenopus laevis tadpoles can regrow their tails throughout their life before metamorphosis, except for a brief period (NF Stage 46 and 47) where amputations result in no regeneration. (Bottom) Example schematics depicting the tadpole morphology and their regeneration status. (B) Xenopus laevis tadpoles can regrow their limbs but lose this ability during their development. (Bottom—Left) Example schematics depicting the tadpole limb morphology and amputation outcomes. (Bottom—Right) Schematics describing differences in froglets and adults and their amputation outcome. (C) (Top) Mice can regrow their lost distal digit tips throughout their life. (Bottom) Schematics for animal morphologies. Green bars indicate the level of regenerative capacity with a wide green bar demonstrating that the animal is regeneration competent. Small bars indicate a loss of regenerative capacity and the fading green bar represents the gradual reduction in regenerative ability.

Figure 2. Xenopus limb and mouse digit tip regeneration has positional biases. (A) (Top) Xenopus limb amputations (NF Stage 54–58) to bone result in greater deficits in regeneration (e.g. more missing digits) compared to joint amputations. (Bottom) Xenopus limb amputations (NF Stage 54–58) to proximal regions, which remove more of the limb, result in worse regenerative outcomes (e.g. more missing digits) compared to distal amputations. (B) Mice can regrow distal digit tips, but fail to regenerate upon amputations that remove the nail entirely. Throughout the figure, red arrows indicate the amputation positions resulting in less or no regeneration, compared to blue arrow indicated positions.

References [+] :

Abrams, A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice. 2021, Pubmed