Conserved anterior/posterior tissue asymmetry encodes proximal/distal positional information during axolotl limb regeneration.

Authors

Alexander J Trostle, Matthew A Cherubino, Dimitri Sokolowskei, Mimi C Sammarco, Catherine D McCusker, Robert J Tower

Published in

Cell reports. Volume 45. Issue 7. Pages 117669. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

While mammalian limb regeneration is limited to the distal fingertips, axolotls can regenerate entire limbs, providing a model system to uncover conserved patterning mechanisms. Although anterior-posterior (A/P) signaling is required for limb regeneration, how A/P patterning is coordinated across limb segments remains unclear. Using spatial transcriptomics and our SpatialFlux analysis pipeline, we found that A/P genes are asymmetrically distributed along the proximal-distal (Pr/Di) axis of both uninjured and regenerating axolotl limbs. This asymmetric boundary coincides with distally enriched AP-1 and ERK signaling, with ERK inhibition disrupting both posterior and distal patterning programs, linking A/P organization to Pr/Di positional identity. Remarkably, a similar asymmetric boundary is present in fetal human limbs, revealing an evolutionarily conserved patterning paradigm. These findings challenge the long-standing model of a symmetrical A/P limb midline boundary and support a revised model, in which shifting A/P ratios regulate Pr/Di patterning.

PMID:
42446998
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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