Regeneration in Reptiles Generally and the New Zealand Tuatara in Particular as a Model to Analyse Organ Regrowth in Amniotes: A Review

Abstract

The ability to repair injuries among reptiles, i.e., ectothermic amniotes, is similar to that of mammals with some noteworthy exceptions. While large wounds in turtles and crocodilians are repaired through scarring, the reparative capacity involving the tail derives from a combined process of wound healing and somatic growth, the latter being continuous in reptiles. When the tail is injured in juvenile crocodilians, turtles and tortoises as well as the tuatara (Rhynchocephalia: Sphenodon punctatus, Gray 1842), the wound is repaired in these reptiles and some muscle and connective tissue and large amounts of cartilage are regenerated during normal growth. This process, here indicated as “regengrow”, can take years to produce tails with similar lengths of the originals and results in only apparently regenerated replacements. These new tails contain a cartilaginous axis and very small (turtle and crocodilians) to substantial (e.g., in tuatara) muscle mass, while most of the tail is formed by an irregular dense connective tissue containing numerous fat cells and sparse nerves. Tail regengrow in the tuatara is a long process that initially resembles that of lizards (the latter being part of the sister group Squamata within the Lepidosauria) with the formation of an axial ependymal tube isolated within a cartilaginous cylinder and surrounded by an irregular fat-rich connective tissue, some muscle bundles, and neogenic scales. Cell proliferation is active in the apical regenerative blastema, but much reduced cell proliferation continues in older regenerated tails, where it occurs mostly in the axial cartilage and scale epidermis of the new tail, but less commonly in the regenerated spinal cord, muscles, and connective tissues. The higher tissue regeneration of Sphenodon and other lepidosaurians provides useful information for attempts to improve organ regeneration in endothermic amniotes.

Tail regeneration in the gecko Sphaerodactylus argus shows that the formation of an axial elastic skeleton is functional for the new tail

“…Lizards and the tuatara are able to regenerate large volumes of cartilage tissues in the tail, joints and vertebrae (Alibardi & Sala, 1981; Alibardi & Meyer‐Rochow, 1989, 2021; Alibardi, 2015; Alibardi, 2021; Lozito & Tuan, 2015, 2016a,b). In some geckos, like most lizards not specifically adapted to an arboreal life, the regenerated cartilage is mainly hyaline and the new tail quite stiff (Boring et al, (1948–49); Furieri, 1956; McLean & Vickaryous, 2011; Mufty & Iqbal, 1975; Shah & Chakko, 1968; Werner, 1967).…”

“…Further studies (Lozito & Tuan, 2016a,b) shown that the two processes are orchestrated by a different mechanism, (1) the proximal chondrogenesis and mineralization from the activity of BMP‐2 and Ihh while (2) the distal chondrogenesis and mineralization derive from the stimulation of Shh secreted from the regenerating ependyma on the surrounding cells of the blastema. In the regenerating tail cartilage of the tuatara ( Sphenodon punctatus ), differently from that of lizards so far analysed, the calcification of the cartilaginous cylinder occurs centrally and not in outer and inner ring‐like peripheral regions (Alibardi & Meyer‐Rochow, 2019, 2021). The mechanism of this different pattern of growth and calcification remains unexplained but is somehow correlated to the long period of time required for tail regeneration in the tuatara that overlaps with its natural growth (Alibardi & Meyer‐Rochow, 1989, 2019, 2021).…”

“…In the regenerating tail cartilage of the tuatara ( Sphenodon punctatus ), differently from that of lizards so far analysed, the calcification of the cartilaginous cylinder occurs centrally and not in outer and inner ring‐like peripheral regions (Alibardi & Meyer‐Rochow, 2019, 2021). The mechanism of this different pattern of growth and calcification remains unexplained but is somehow correlated to the long period of time required for tail regeneration in the tuatara that overlaps with its natural growth (Alibardi & Meyer‐Rochow, 1989, 2019, 2021). The prevalent production of collagen II or other types of collagens (Lozito & Tuan, 2015, Lozito & Tuan, 2016a,2016b) precedes the mineralization or the direct ossification in the outer and inner ring‐like regions of the proximal cartilaginous tube, determining stiffness in the regenerated tail.…”

“…Among amniotes, lizards are a noteworthy exception with respect to the general scarring outcome deriving from wounding or organ amputation. Numerous lizards and the New Zealand tuatara can regenerate a large organ, the tail, composed of numerous and integrated tissues, although anatomically simpler than the original tail (Alibardi, 1994,1995a,b, 2021; Alibardi & Meyer‐Rochow, 2021; Bellairs & Bryant, 1985; Fisher et al, 2012; Gilbert et al, 2013; Jacyniak et al, 2017; Lozito & Tuan, 2015, 2016a,b; Palade et al, 2018; Quattrini, 1954). The new tail is also functionally less performing than the original tail in most lizards, with limited bending capability mainly due to the replacement of the segmented vertebral column with an almost continuous cartilaginous tube (Alibardi & Sala, 1981; Alibardi & Meyer‐Rochow, 1989; Alibardi, 1995a, 2015; Londono et al, 2017; Lozito & Tuan, 2015, 2016a).…”

Introduction to the Study on Regeneration in Lizards as an Amniote Model of Organ Regeneration

“…In addition to histological and histochemical studies, these investigators also conducted numerous biochemical analyses and enzymatic studies to obtain a broad picture of the metabolism of regenerating tails in geckos and scincid lizards. Several other histological and histochemical studies have been derived from African, Australian, and Caribbean geckos and scincids [ 18 , 19 , 20 , 21 ], and from the New Zealand tuatara [ 11 , 22 , 23 , 24 , 25 ].…”