Publication

Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration

2026

Abstract

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.

Official source

https://infoscience.epfl.ch/entities/publication/0a63b2bd-1f39-4479-813c-7cabc2a2750c

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2026

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/0a63b2bd-1f39-4479-813c-7cabc2a2750c

About this result

Related concepts (32)

Regeneration (biology)

In biology, regeneration is the process of renewal, restoration, and tissue growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. Regeneration can either be complete where the new tissue is the same as the lost tissue, or incomplete after which the necrotic tissue becomes fibrosis.

Limb development

Limb development in vertebrates is an area of active research in both developmental and evolutionary biology, with much of the latter work focused on the transition from fin to limb. Limb formation begins in the morphogenetic limb field, as mesenchymal cells from the lateral plate mesoderm proliferate to the point that they cause the ectoderm above to bulge out, forming a limb bud. Fibroblast growth factor (FGF) induces the formation of an organizer at the end of the limb bud, called the apical ectodermal ridge (AER), which guides further development and controls cell death.

Frog

A frog is any member of a diverse and largely carnivorous group of short-bodied, tailless amphibians composing the order Anura (ἀνούρα, literally without tail in Ancient Greek). The oldest fossil "proto-frog" Triadobatrachus is known from the Early Triassic of Madagascar, but molecular clock dating suggests their split from other amphibians may extend further back to the Permian, 265 million years ago. Frogs are widely distributed, ranging from the tropics to subarctic regions, but the greatest concentration of species diversity is in tropical rainforest.

Related publications (5)

Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration

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