Tail regeneration in Lepidosauria as an exception to the generalized lack of organ regeneration in amniotes

Abstract

The present review hypothesizes that during the transition from water to land, amniotes lost part of the genetic program for metamorphosis utilized in larvae of their amphibian ancestors, a program that in extant fish and amphibians allows organ regeneration. The direct development of amniotes, with their growth from embryos to adults, occurred with the elimination of larval stages, increases the efficiency of immune responses and the complexity of nervous circuits. In amniotes, T‐cells and macrophages likely eliminate embryonic‐larval antigens that are replaced with the definitive antigens of adult organs. Among lepidosaurians numerous lizard families during the Permian and Triassic evolved the process of tail autotomy to escape predation, followed by tail regeneration. Autotomy limits inflammation allowing the formation of a regenerative blastema rich in the immunosuppressant and hygroscopic hyaluronic acid. Expression loss of developmental genes for metamorphosis and segmentation in addition to an effective immune system, determined an imperfect regeneration of the tail. Genes involved in somitogenesis were likely lost or are inactivated and the axial skeleton and muscles of the original tail are replaced with a nonsegmented cartilaginous tube and segmental myotomes. Lack of neural genes, negative influence of immune system, and isolation of the regenerating spinal cord within the cartilaginous tube impede the production of nerve and glial cells, and a stratified spinal cord with ganglia. Tissue and organ regeneration in other body regions of lizards and other reptiles is relatively limited, like in the other amniotes, although the cartilage shows a higher regenerative capability than in mammals.

When one tail isn't enough: abnormal caudal regeneration in lepidosaurs and its potential ecological impacts

“…The ability to regenerate tissue is often, but not exclusively, coupled with autotomy (Lozito & Tuan, 2017;Alibardi, 2019;Emberts et al, 2019;Barr et al, 2019b). Evolving and being lost multiple times across taxonomic levels, autotomy and regeneration capacity is significantly influenced by both abiotic and biotic factors (Alibardi, 2017(Alibardi, , 2019Emberts et al, 2019).…”

“…The ability to regenerate tissue is often, but not exclusively, coupled with autotomy (Lozito & Tuan, 2017;Alibardi, 2019;Emberts et al, 2019;Barr et al, 2019b). Evolving and being lost multiple times across taxonomic levels, autotomy and regeneration capacity is significantly influenced by both abiotic and biotic factors (Alibardi, 2017(Alibardi, , 2019Emberts et al, 2019). Lepidosaurs represent an evolutionary mid-point, a terrestrial clade that lack a moulting or metamorphosis stage, often a point of regeneration in other taxa, but have not yet developed an immune and healing system as efficient as that of higher amniotes such as mammals where fast healing through the formation of scar tissue is prioritised over regeneration (Alibardi, 2017(Alibardi, , 2019.…”

“…Evolving and being lost multiple times across taxonomic levels, autotomy and regeneration capacity is significantly influenced by both abiotic and biotic factors (Alibardi, 2017(Alibardi, , 2019Emberts et al, 2019). Lepidosaurs represent an evolutionary mid-point, a terrestrial clade that lack a moulting or metamorphosis stage, often a point of regeneration in other taxa, but have not yet developed an immune and healing system as efficient as that of higher amniotes such as mammals where fast healing through the formation of scar tissue is prioritised over regeneration (Alibardi, 2017(Alibardi, , 2019. In lizard taxa with intra-vertebral breakage planesthe more ancestral conditiona broken tail regenerates over time with the bony vertebrae being replaced by a rigid cartilage rod (Woodland, 1920;Bellairs & Bryant, 1985).…”

Appendage regeneration in anamniotes utilizes genes active during larval‐metamorphic stages that have been lost or altered in amniotes: The case for studying lizard tail regeneration

“…This wonder further increased observing that also numerous internal organs, aside body appendages, could largely regenerate (Table 1). Unfortunately, the biology, evolution and ecology of the vertebrates with so different regenerative ability have been generally neglected or completely ignored (Alibardi, 2017a(Alibardi, , 2018a(Alibardi, , 2018b(Alibardi, , 2019a(Alibardi, , 2019b(Alibardi, , 2019c(Alibardi, , 2020aGrygorian, 2016;Scadding, 1977Scadding, , 1981. Even today, cell and molecular studies do not consider regeneration as an evolutionary process, and that the most competent regenerating vertebrates, fish and amphibians, have evolved specific eco-physiological and developmental processes in advance from their terrestrial-derived species.…”

“…Aside other genes, mammalian genomes contain genes absent in lower vertebrates and numerous new immune genes (Villanueva-Canas, Ruiz-Orera, Agea, Andreu, & Mar Alba, 2017). The more effective acquired immune system of amniotes appears detrimental for the regeneration of complex organs (Alibardi, 2019a(Alibardi, , 2019b(Alibardi, , 2020aHarty et al, 2003;Mescher et al, 2016;Zimmerman, Vogel, & Bowden, 2008). The contemporaneous presence of genes for adaptive immunity, complex nervous circuits, or for other amniote functions somehow determines regeneration failure, as schematically indicated in Figure 5b,c.…”