Can Aztekin (Friedrich Miescher Laboratory, MPI Tübingen)

Signaling centers of appendage regeneration: from frogs to mammals

Host: Sara Wickström

Why mammals cannot regrow their lost limbs remains one of the biggest mysteries in biology. Unlike mammals, Xenopus laevis tadpoles possess a remarkable ability to regenerate lost appendages. In our previous work (Aztekin et al., Science, 2019; Development 2021), we identified key signaling-center cell types that orchestrate amphibian tail and limb regeneration. Through cross-species comparisons (Zhong et al., Nature Communications 2023), we identified equivalent cell populations in mammals and developed simplified mammalian stem cell–based models, including limb bud organoids, to investigate the properties of these regenerative cells (Skoufa et al., Science Advances 2025). In this talk, I will present our recent findings comparing frog tadpoles and embryonic mouse limbs, revealing that regenerative amphibians exhibit reduced oxygen sensing. This altered oxygen sensitivity shapes cellular biomechanical, epigenetic, and metabolic states that are conducive to regeneration initiation. In contrast, mammalian limbs exhibit heightened oxygen sensitivity. However, altering environmental oxygen levels rewires mouse limbs toward a tadpole-like regenerative state and induces regeneration initiation (Tsissios et al., Science 2026).Together, these results reveal a conserved mechanism underlying limb regeneration initiation across species and suggest potential pathways for reactivating this dormant capacity in mammals.

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