Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration
Summary
Why mammals cannot regenerate limbs like amphibians do presents a long-standing puzzle in biology. To uncover the underlying differences, we compared amputation responses of embryonic mouse (Mus musculus) and Xenopus laevis tadpole limbs. Lowering environmental oxygen or stabilizing the oxygen-sensitive hypoxia-inducible factor 1A (HIF1A) induced rapid wound healing in mouse limbs. This response was accompanied by altered cellular mechanics, metabolism, and a histone landscape that primed
Content
# Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration
*Published: 2026 Apr 9*
Why mammals cannot regenerate limbs like amphibians do presents a long-standing
puzzle in biology. To uncover the underlying differences, we compared amputation
responses of embryonic mouse (Mus musculus) and Xenopus laevis tadpole limbs.
Lowering environmental oxygen or stabilizing the oxygen-sensitive
hypoxia-inducible factor 1A (HIF1A) induced rapid wound healing in mouse limbs.
This response was accompanied by altered cellular mechanics, metabolism, and a
histone landscape that primed regenerative cell states. Conversely, Xenopus
tadpole limbs retained these features even under high oxygen levels. Their
reduced oxygen-sensing capacity was associated with decreased HIF1A-regulating
gene expression. Our results thus identify species-specific oxygen-sensing
capacity as a fundamental, targetable mechanism that can unlock latent
regenerative programs in mammals.
DOI: 10.1126/science.adw8526