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Figure 3 Comparative anatomy of regenerating appendages in lizard, salamander, and zebrafish. (A) Amputation or autotomy of lizard tail induces the formation of a cone-like shaped blastema, covered by a thick wound epidermis that will form the apical epidermal peg(AEP), whose correspondence to the apical epidermal cap (AEC) found in amphibians and fish is still uncertain. During blastema formation, likely in response to AEP signals, the central canal of the original spinal cord, the ependymal tube, elongates and infiltrates the proliferating tail blastema. (B) After amputation of salamander limb, the wound epidermis quickly covers the stump. Within days, the wound epithelium becomes innervated, thickens, and becomes a specialized AEC. The AEC induces dedifferentiation in the underlying stump tissue and attracts cells, which accumulate below the AEC to form the blastema. Modified from Payzin-Dogru and Whited, 2018. (C) After zebrafish fin amputation, epithelial cells migrate to cover the wound, forming the AEC. Under the AEC, stump tissues dedifferentiate to form the blastema. Within 24 h, blastemal cells segregate into two compartments: the distal blastema, populated by slowly proliferating cells, and the proximal blastema, in which cells rapidly proliferate and differentiate to replace the amputated tissue. Dotted lines indicate the site of amputation/autotomy.