Fig. 3.

Key processes during limb regeneration. The salamander limb contains all typical structural elements of tetrapods. Upon amputation, salamander limb regeneration starts by scar-free wound healing and wound closure. Infiltrating macrophages are essential for this event, probably for clearing debris, although other signalling mechanisms cannot be excluded. Cells in the mature limb then undergo reprogramming/dedifferentiation to form a blastema. The degree of reprogramming varies between cell types and species. Nerve-derived factors are required for subsequent blastema cell proliferation and outgrowth. The cells also retain positional memory during the regeneration event, allowing them to undergo the appropriate patterning to re-from an intact limb. The time course of regeneration indicated in this figure is based on staging in adult Notophthalmus viridescens.