Retinoic acid breakdown is required for proximodistal positional identity during amphibian limb regeneration

Limb regeneration in salamanders involves cells dedifferentiating and migrating to the amputation site to form a blastema. These cells possess positional information to rebuild the limb correctly. Retinoic acid (RA) is known to specify proximal limb identity, but how RA signaling levels are established in the blastema is unknown. This study shows that RA breakdown via CYP26B1 is essential for determining RA signaling levels within blastemas.

• 1
  CYP26B1, an enzyme that breaks down retinoic acid, is more highly expressed in distal blastemas (DBs) than proximal blastemas (PBs).
• 2
  Inhibiting CYP26B1 in DBs increases RA signaling and reprograms distal blastemas into a more proximal identity, causing duplications of proximal limb segments.
• 3
  Shox, an RA-responsive gene, is required for endochondral ossification of stylopodial and zeugopodial skeletal elements during regeneration, but not for limb regeneration itself.