Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Ambystoma mexicanum / injuries
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Ambystoma mexicanum / physiology*
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Amputation, Traumatic / metabolism
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Animals
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Cell Cycle / genetics
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Cell Proliferation / genetics
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Cloning, Molecular
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Extremities / injuries
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Extremities / physiology*
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Muscle Fibers, Skeletal / cytology
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Muscle Fibers, Skeletal / physiology
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Myristoylated Alanine-Rich C Kinase Substrate
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Notophthalmus viridescens / genetics
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Notophthalmus viridescens / injuries
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Notophthalmus viridescens / physiology
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Regeneration / physiology*
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Tail / cytology
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Tail / injuries
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Tail / physiology
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Wound Healing / physiology
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Xenopus
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Zebrafish
Substances
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Intracellular Signaling Peptides and Proteins
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MARCKS protein, human
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Marcks protein, mouse
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Membrane Proteins
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Myristoylated Alanine-Rich C Kinase Substrate