Cell proliferation in the amputated limb of lizard leading to scarring is reduced compared to the regenerating tail

Abstract

After amputation, the tail of lizards regenerates while the limb forms a short scarring outgrowth. Using phospho‐histone‐H3 immunohistochemistry the mitotic activity of limb tissues at 12–25 days after amputation has been studied, when a limb outgrowth of 0.5–2 mm in length is covered by wound epidermis and the underlying connective is turning into a dense scar. In comparison with a regenerating tail of 3–5 mm in length, the number of dividing cells is reduced of 40–70% in different tissues of the scarring limb 1–2 mm in length at 18 days postamputation. Dividing cells are still present at 12–25 days postamputation in the cartilaginous epiphyses of the transected tibia and fibula and of the untransected femur. Also, the injured muscles present at the base of the scarring outgrowth still contain sparse dividing cells after 25 days postamputation of the limb. Together previous studies, the present observations suggest that after the initial proliferation of fibroblasts deriving from the injured tissues, especially from the dermis and intermuscle connectives during the initial 7–15 days postinjury, these cells cover the injured tissues underneath the wound epidermis, but rapidly produce high levels of collagen turning the initial blastema into a scar.

FGFs Treatment on Amputated Lizard Limbs Stimulate the Regeneration of Long Bones, Opening New Avenues for Limb Regeneration in Amniotes: A Morphological Study

“…The histological and immunofluorescent study indicated the formation of an Apical Epidermal Peg (AEP) or a papillated wound epidermis in the apical front of the regenerating limbs (Figures 3 and 4). This result suggests that FGFs administration can stimulate the formation of epidermal areas similar to the AEP found at the tip of the regenerating tail, the epithelial micro-region essential for regeneration [16,17]. In those cases where limb outgrowths longer than 2.5 mm (6 cases out of 11) were originated within the 40-70 days post-amputation period, the induction of an AEP or of a papillated wound epidermis was observed.…”

Immunodetection of FGF1-2 and FGFR1-2 Indicates that these Proteins Disappear in the Wound Epidermis and Blastema of the Scarring Limb in Lizard

“…18,20 FGF immune labeling tends to disappear later on when the proliferation in the limb decreases and only few tissues such a muscle and cartilageare still repairing. 6,7,17,20 Cell proliferation and FGF immune labeling is also abolished in scarring tails after cauterization, an intervention that drives the tail to form a scar instead of regenerates into a new tail.…”

“…18,20 FGF immune labeling tends to disappear later on when the proliferation in the limb decreases and only few tissues such a muscle and cartilageare still repairing. 6,7,17,20 Cell proliferation and FGF immune labeling is also abolished in scarring tails after cauterization, an intervention that drives the tail to form a scar instead of regenerates into a new tail. [6][7][8]10 The importance of FGFs and FGFRs for lizard regeneration confirms previous observations, 10 and the numerous data available for anamniotes such as amphibians and fish, two groups of vertebrates where tissue and organ regeneration is even higher than in lizards.…”

Proliferating Cells in Knee Epiphyses of Lizards Allow for Somatic Growth and Regeneration after Damage

“…However, also fractured femurs [11] and injured knees of adult lizards [12,13] have shown a broad cartilaginous regeneration, suggesting that these ectothermic amniotes are an important model for studies on cartilage regeneration in vertebrates [9,10,14].…”

“…Regeneration of cartilaginous cells in injured bones and knees of lizards is a remarkable case of cartilage regeneration in amniotes, in comparison to the limited cartilage regeneration detected in mammals [11][12][13][14][15][16][17][18][19][20]. In the latter, the injured periosteum gives rise to a fibro-connective tissue and to some new chondrocytes.…”