Sall Genes and Proteins Activation during Early Tail and Limb Regeneration in the Lizard Podarcis muralis Suggests Dedifferentiation

Abstract

Lizards represent the closest amniotes to mammals able to regenerate many tissues, therefore are useful models for studies of mammalian regeneration. Tail regeneration occurs by stem cells but tissue dedifferentiation may also be involved. When injury damages numerous tissues they may undergo dedifferentiation (re-programming). This was indicated especially in muscles and connectives of the tail 7–10 days postamputation. The transcriptome of regenerating tail and limb from the lizard Podarcis muralis detected upregulation of spalt-like genes (sall 1–4), known to be involved in re-programming. Here, immunolocalization of the sall4 protein and 5BrdU-labeled cells (proliferating) was conducted. A variable number of 5BrdU and sall4-positive cells are detected among stump connective tissues, injured muscles, and dermis. Labeling for sall4 is cytoplasmic and also nuclear, and it is also noted in cytoplasmic muscle fragments. The latter likely derived from the fragmentation of injured muscles in both tail and limb stumps at 7–16 days postamputation. Occasional, isolated sall4-labeled cells are rarely detected in the blastema, and none in the wound epidermis or regenerating spinal cord and muscles. The present study indicates that cell dedifferentiation occurs during early stages of tail and limb amputation in lizards, contributing with activated stem cells to their regeneration or scarring.