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Nature. 2016 Mar 10;531(7593):237-40. doi: 10.1038/nature16974.

MARCKS-like protein is an initiating molecule in axolotl appendage regeneration.

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DFG Research Center for Regenerative Therapies (CRTD), Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Karolinska Institute, Department of Cell and Molecular Biology, Centre of Developmental Biology for Regenerative Medicine, SE-171 77 Stockholm, Sweden.


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 considerable portion of the body part has been removed. 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. A wound-associated molecule that triggers the initial proliferative response to launch regeneration has remained obscure. Here, 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. The identification of a regeneration-initiating molecule opens the possibility of understanding how to elicit regeneration in other animals.

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