New insights into limb regeneration published in Science

A study led by Branco Weiss Fellow Can Aztekin, now at the Max Planck Society, has been published in Science, offering a new explanation for one of biology’s longstanding questions: why some animals can regenerate limbs while mammals cannot.

The research identifies oxygen as a critical switch controlling the early stages of regeneration. Under low-oxygen conditions, cells stabilize a protein known as HIF1A, which initiates rapid wound healing and activates biomechanical, epigenetic, and metabolic programs associated with regeneration. At normal oxygen levels, this process is quickly shut down.

By directly comparing frog tadpoles and mouse embryos, the team demonstrated that mammalian tissues retain a previously underappreciated regenerative potential. When oxygen levels were reduced – or when the oxygen-sensing pathway was experimentally stabilized – mouse cells showed faster wound closure and early signs of entering a regenerative state. The key difference between species lies in how their cells sense oxygen. Regeneration-competent animals maintain stable activation of HIF1A even in oxygen-rich environments, while mammalian cells respond strongly to oxygen and suppress regenerative programs shortly after injury.

The findings suggest that the apparent inability of mammals to regenerate limbs may not be absolute, but instead depends on environmental and cellular conditions. While the study does not demonstrate full limb regrowth in mammals, it outlines a plausible pathway for enhancing regenerative responses in the future. “This work shows that regenerative programs can be triggered in mammalian tissues,” says Aztekin. “It opens a clear and testable path toward promoting regeneration in adult mammals.”

Read the article in Science: https://www.science.org/doi/10.1126/science.adw8526

Read the press release by Max-Planck-Gesellschaft: https://www.mpg.de/26212730/0302-entw-when-oxygen-determines-if-a-limb-can-regrow-151730-x