ArticleNature communications2025
Retinoic acid breakdown is required for proximodistal positional identity during axolotl limb regeneration.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Conserved anterior/posterior tissue asymmetry encodes proximal/distal positional information during axolotl limb regeneration.Cell reports · 2026Article
- tBid-Mediated Genetic Ablation of Connective Tissue Cells Reveals Their Key Regulatory Function During Limb Regeneration in Axolotls.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A characterization of axolotl digit regeneration: conserved mechanisms, divergent patterning, and a critical role for hedgehog signaling.NPJ Regenerative medicine · 2026Article
- The cellular logic of limb regeneration.eLife · 2026Article
- Comparative multi-omic analysis reveals conserved and derived mechanisms of fin and limb regeneration.Nature communications · 2026Article
- Regenerate to "Rejuvenate": Insights From Adult Resident Stem Cells of Aged Flatworms and Mice.Aging cell · 2025Review
- The subfunctionalization ofFrontiers in cell and developmental biology · 2025Article
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9 authors.
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Abstract
Regenerating limbs retain their proximodistal (PD) positional identity following amputation. This positional identity is genetically encoded by PD patterning genes that instruct blastema cells to regenerate the appropriate PD limb segment. Retinoic acid (RA) is known to specify proximal limb identity, but how RA signaling levels are established in the blastema is unknown. Here, we show that RA breakdown via CYP26B1 is essential for determining RA signaling levels within blastemas. CYP26B1 inhibition molecularly reprograms distal blastemas into a more proximal identity, phenocopying the effects of administering excess RA. We identify Shox as an RA-responsive gene that is differentially expressed between proximally and distally amputated limbs. Ablation of Shox results in shortened limbs with proximal skeletal elements that fail to initiate endochondral ossification. These results suggest that PD positional identity is determined by RA degradation and RA-responsive genes that regulate PD skeletal element formation during limb regeneration.
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