Three Distinct Phases of Regeneration-Specific Gene Expression in the Axolotl Blastema

The salamander has the remarkable ability to regenerate its limb after amputation. Cells at the site of amputation form a blastema and then proliferate and differentiate to regrow the limb. To better understand this process, we have performed deep RNA sequencing of the blastema over a time course. We find genes expressed in three phases with a prominent burst in oncogene expression during the first day, blastemal/limb bud genes peaking at 7 to 14 days, and markers for terminal differentiation upregulated later. We compare these expression patterns to those in a mouse digit amputation model to identify genes specific to the regenerative response. We find that limb patterning genes, SALL genes, and genes involved in the proteasome, adult stem cell, embryonic stem cell, retinoid metabolism, and WNT and NOTCH signaling are regeneration-specific. We establish the “Axolomics” Database, which provides a tool for depositing, retrieving, and searching axolotl-related “omic” information.