Review: Cell and Molecular Biology of Healing in Amputated Limbs of the Lizard <i>Podarcis muralis</i> Reveal a Gene Activation Program for Scarring

ABSTRACT The present review summarises cell biology and transcriptome data describing cell and extracellular matrix reaction to the injury in the amputated lizard limb and its poor regeneration. Immuno‐electron microscopy indicates massive penetration of immune cells among injured tissues during the first 1–3 weeks post‐amputation. Injured connective tissues, muscles, bone, and cartilaginous tissues undergo a process of dedifferentiation. Numerous proliferating fibroblasts derive from the injured tissues, but muscles and cartilage are repaired without further growth of repaired myofibers. A dense connective tissue is later formed, leaving a scar‐like outgrowth that becomes scaled. Aside from chondrocytes proliferation from the injured bone with alcian‐blue positive matrix for acidic glycosaminoglycans, no alcianophilic matrix is formed in connectives of the scarring limb. The up‐regulated genes coding for extracellular matrix proteins during this period reveal the production of specific collagens, enzymes, and matrix proteins whose function determines a scarring program of differentiation. No transcriptome data are available for lizard developing limbs, so no comparison with the scarring limb is possible. Limb tissues in lizards undergo a process of dedifferentiation for repairing but cannot regenerate large masses of new tissues into a functional new limb. These reptiles provide useful comparative information for studies on amniotes regeneration.