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 Right Foot Forward

Retinoic acid plays a key role in proximodistal positional identity in axolotl limb regeneration

05 July 2025

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

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