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We compared frog tadpole and embryonic mouse limbs for their ability to initiate regeneration. This comparison revealed that species-specific differences in oxygen-sensing pathways influence key biomechanical, epigenetic, and metabolic programs required for regeneration. Our findings identify oxygen sensing as an evolutionarily tunable control point for limb regeneration and provide experimental evidence for why mammals may have lost this ability and how it might be reactivat

In this review, Can synthesizes evidence showing that regeneration does not simply replay development, but instead could follow context-dependent cellular behaviours shaped by injury and tissue state. This reframes regeneration as a distinct biological process. https://journals.biologists.com/dev/article/151/14/dev202541/361236

We developed a mouse embryonic stem cell–based protocol that generates limb development and regeneration-related skin cell types and 3D mesodermal organoids with limb-bud–like features. Our approach enables unprecedented quantitative analysis of regenerative skin cell properties and provides a controllable system to dissect how these cells can influence cell fate and spatial organization. https://www.biorxiv.org/content/10.1101/2024.07.02.601324v1