Salamander limb regeneration proliferation is dependent on:
Axolotl limb blastema proliferation and formation depend absolutely on nerve presence providing trophic factors. Denervated limbs after amputation fail to form blastema, undergo fibrosis. Nerves supply FGF2, neuregulin, BMP, anterior gradient protein nAG, maintain apical epidermal cap expression of FGF8 and Wnt5a, prevent differentiation. Accessory limb model demonstrates sufficient nerve fibers diverted to wound plus skin graft induces ectopic blastema without amputation. Molecularly nerve signals activate blastema cell cycle, sustain Myc and maintain MMP activity degrading matrix. Hence limb
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 21: Nerve dependence of salamander limb regeneration and proliferation.