Spinal ganglia and peripheral nerves innervating the regenerating tail and muscles of lizards

The present review summarizes available information on the contribution of regenerating nerves to the process of regeneration in the tail of lizards. From the last three segments of the spinal cord and ganglia proximal to the regenerating tail, motor, sensory somatic and autonomous nerves regenerate and richly innervate the growing blastema. However, experimental studies have indicated that peripheral nerves are not essential for stimulating the regeneration of the tail that instead is mainly sustained by the interaction of the apical ependyma with the wound epidermis. Ganglion neurons innervating the regenerating blastema increase their size and some satellite cells multiply but no ganglion neurons are regenerated. Numerous Schwann cells proliferate to keep pace with nerve regeneration, and they form myelin starting from 3 to 4 weeks of tail regeneration. The hypertrophic ganglion neurons synthesize growth factors and signaling proteins such as FGFs and Wnts that are transported into the regenerating blastema through the regenerating nerves. Nerves form synaptic-like contacts with mesenchymal cells or fibroblasts at the tip of the regenerating blastema but not synaptic boutons. These terminals may discharge stimulating factors that favor cell proliferation but this is not experimentally demonstrated. Most of the innervation is directed to differentiating muscles where nerve endings form cholinergic motor-plates. Transcriptome data on the regenerating blastema-cone detect up-regulation of various genes coding for ionic channels, neurotransmitter receptors and signaling proteins. The latter suggests that the neurotrophic stimulation may control cell proliferation but is most directed to the functionality of regenerating muscles.