Right Foot Forward

If your toe got chopped off, you wouldn’t want a whole foot to grow back in its place. Neither would an axolotl, whose remarkable limb regeneration powers make this a more real possibility. Regenerating limbs retain their ‘proximodistal identity’ (ie. how far away they are from the body) thanks to genes that guide cells in the growing stump. Retinoic acid is known to regulate these genes, but how its levels are managed is unclear. Researchers hoping that axolotl biology could hold clues to improving human tissue repair discovered that the rate of retinoic acid breakdown is key. Reducing this breakdown led to structural errors, like regenerating the wrong limb segments (middle row), while fully blocking it caused regeneration to fail altogether (bottom). Understanding how positional identity is established is fundamental to tissue engineering and could even let us help the body repair and regrow without putting a foot wrong.

Written by Anthony Lewis

Anthony Lewis

Writer

Ant was the web editor in the early days of BPoD, and has since worked with the UK’s top science organisations as a writer and multimedia producer. He now splits his time between freelance work and managing multimedia at The Lancet.

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• Picture is a compilation of image panels from work by Timothy J. Duerr and colleagues
• Northeastern University, Department of Biology, Boston, MA, USA
• Image originally published with a Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
• Published in Nature Communications, June 2025