The cellular and signaling dynamics of salamander limb regeneration

Limb amputation in salamanders yields a wound response that ultimately leads to replacement of the missing part. This unique-among-tetrapod trait involves the migration and recruitment of multiple cell types including epithelium, immune cells, axonal growth cones, and connective tissue cells to build the blastema which contains the proliferating stem and progenitor cells to rebuild the limb tissues. A number of the signaling and cell biological events have been defined. They point to the intimate coordination of physical events such as osmotic pressure, cell migration, and cell-cell communication with changes in cell identity such as dedifferentiation into embryonic-like epithelial and mesenchymal cells.