Neural regulation of H3K27me3 during the induction of patterning competency in regenerating Axolotl limb cells.

Limb regeneration in the Mexican axolotl relies on the dedifferentiation of mature limb cells into blastema cells, which gain the ability to respond to patterning signals that guide tissue regeneration. While limb nerves are essential to make the blastema cells competent to pattern, the mechanisms remain unclear due to the complex and overlapping signals in amputated limbs. To overcome this challenge, we developed the Competency Accessory Limb Model (CALM), a simplified limb regeneration assay to study the induction and maintenance of patterning competency. Using CALM, here we show specific temporal windows during which cells acquire competency and associate this state with distinct H3K27me3 chromatin signatures. Furthermore, a combination of FGF and BMP signaling is sufficient to induce patterning competency in limb wound cells, and the ErBB signaling pathway is a downstream epigenetic target of these signals. These findings offer new insights into the molecular regulation of regenerative patterning.