MARCKS-Like Protein is an Initiating Molecule in Axolotl Appendage Regeneration

Identifying key molecules that launch regeneration has been a long sought goal. Multiple regenerative animals show an initial wound-associated proliferative response that transits into sustained proliferation if a significant portion of the body part has been removed (1-3). In the axolotl, appendage amputation initiates a round of wound-associated cell cycle induction followed by continued proliferation that is dependent on nerve-derived signals (4,5). A wound-associated molecule that triggers the initial proliferative response to launch regeneration has remained obscure. Using an expression cloning strategy followed by in vivo gain- and loss-of-function assays, we identified axolotl MARCKS like Protein (MLP) as an extracellularly released factor that induces the initial cell cycle response during axolotl appendage regeneration.