User:CMSRegenBio/sandbox

From Wikipedia, the free encyclopedia

Lizard tail regeneration is the process by which some lizards grow new tails after their original tail has been lost. It is most often studied in the Carolina Anole and the Leopard Gecko.

Morphology and Structure[edit]

Morphology of a regenerating lizard tail

Lizard tail regeneration is an example of imperfect limb regeneration, similar in many ways to regeneration phenomena observed in Xenopus and other amphibians.[1][2][3] Regenerated lizard tail morphology is unlike normal lizard tail morphology, to the extent that a section of regenerated lizard tail can be distinguished by eye from the original tissue. Increased rigidity and stark scale discoloration in the regenerated tail section are both common among specimens caught in the wild.[4]

Cartilage Tube[edit]

Regenerated lizard tails are made up of a single, unsegmented cartilage tube rather than individual vertebrae.[5] This results in an observable loss of tail flexibility,[4] which often leads to impairment of the lizard's overall mobility.[6][7] The regenerated cartilage tube is made up of two distinct sections:[8] proximal cartilage tube, which undergoes ossification typical of amphibian regeneration;[3] and distal cartilage tube, which calcifies and is easily distinguishable from the proximal cartilage tube.[4]

Nerve and Spinal Cord[edit]

The cartilage tube surrounds the regenerated spinal cord, which is anatomically similar to the original spinal cord and serves to innervate the regenerated muscle fiber. It consists of a central canal lined with ependymal cells and surrounded by a "disorganized mass" of descending neurons and radial glial cells.[9]

All nerves in the regenerated tail are descended from the remaining nerves from the remaining tail spinal cord,[10] and no new nerve cell bodies are formed during lizard tail regeneration.[11] Ascending nerves do not regenerate.[11] Additionally, a greater than average proportion of nerves in regenerated lizard tail are unmyelinated.[11]

Muscle Fiber[edit]

Muscle bundles in the regenerated tail are non-uniform in size and lack some of the organization seen in the original tail.[12] Connective tissue is also increased in regenerated muscle, and in some tails replaces all skeletal muscle in select muscle bundles.[12]

Functionality[edit]

Despite its anatomical imperfections, lizard tail regeneration restores much of the functionality of the original limb, including musculature and innervation.[12] Notably, regenerated lizard tail remains capable of re-regeneration following subsequent amputations.[8] By contrast, most mammals cannot heal or regenerate cartilage whatsoever.[13]

Imperfect tail regeneration can be an advantage or disadvantage depending on the species of lizard. For example, both male and female Agama agama who suffer caudal injuries regenerate thick, cartilaginous, club-like tails, which males use to compete with one another for social status and mates.[14]

Biological Processes[edit]

Blastema[edit]

One of the hallmarks of the regenerative process is the blastema, a collection of cells formed at the site of amputation capable of regenerating the tissue lost from the lizard. The blastema is a tissue of interest as scientists continue to investigate the underlying biological processes of the lizard tail and is a common feature present in many other regenerating organisms.

Histological diagram of the early stages of tail regeneration in the leopard gecko.[15]

Wound epithelium[edit]

After the tail is lost, the lizard must first heal the wound in a scar-free manner. Scar-free healing generally means that there is not the collagen and other scar structures that lead to permanent alterations in the tissue at the wound site and tend to obstruct regeneration. Scar-free healing results in the wound epithelium at the site of amputation. There is blood clotting to prevent bleeding, formation of the wound epithelium, and formation of the blastema. The lizard is therefore and example of epimorphic regeneration, a process by which the site of amputation is where the source of proliferating cells will reside. The wound epithelium is necessary for regeneration, as its removal inhibits regeneration.[15]

Nerve Dependence in Regeneration[edit]

The blastema, however, is not the sole contributing tissue of the regenerative process in lizards. For a long time, scientists studying regeneration knew that the nerves that reside in the limb play a part in regeneration of newts, with regeneration based on the number of nerve fibers present.[16] This nerve dependence in regeneration was carried over to the lizard tail by performing similar analyses to prove that lizards do indeed rely upon the nerves of the tail to carry out proper regeneration. In contrast to the newt though, it was shown that lizard tail regeneration was not reliant upon the peripheral nerves like in the limb, but more so on the ependyma, a component of the central nervous system in the lizard.[17]

Lizards lacking tail spinal cord or ependyma at the site of tail loss fail to regenerate their tails.[18] This phenomenon is also observed in salamanders, which retain their tail spinal cord into adulthood, whereas vertebrates that are not capable of tail regeneration do not possess tail spinal cords as adults.[19] Furthermore, transplants of ependymal or spinal cord tissue onto undamaged lizard tails have been demonstrated to cause ectopic tail growth,[20] resulting in lizards with more than one fully functional tail.

Transcriptomics[edit]

Like many biological processes, lizard tail regeneration occurs as a process involving the lizard’s genes. All cells of the lizard contain the same genome, or sequence of DNA that codes for the production of specific RNA, which will ultimately result in the production proteins that dictate how the cells of the lizard function. Using methods like RNA sequencing, scientists have been able to identify some key genes expressed by cells in the regenerated lizard tail by means of sequencing the transcriptome.[21]

Wound Response

The presence process of wound response is an intuitive finding, given that regeneration tends to occur in response to severe tail wounding. The genes found that have known roles in the wound response include (but are not limited to): igfbp4, mdk, ptx3, and pdgfra. Many genes of the Wnt signaling pathway, a recurring signaling pathway in the processes of regeneration and development.[21]

Hormonal Regulation

Hormonal regulation is a biological process that can affect growth and development in many organisms.[22] It would follow reason, then, that the genes regulating the behavior and pathways of the hormones would be components that are key in regeneration. The genes identified in the lizard tail that are involved in hormonal regulation include: ednra, edn3, pcsk1, rab8b, ptx3, f2r, thy1, tnfrsf11b, f2r, spp1, cga, and dio2.[21]

Embryonic Morphogenesis

The process of regeneration in many organisms seems to model the embryonic development of the tissues in the regenerating limb.[23] The genes identified in the lizard tail that are known to be involved in embryonic morphogenesis include (but are not limited to): wnt5a, tnfrsf11b, pdgfra, ror2, mepe, cbfb, igfbp4, spp1, twis, ednra, fgfr4, sall1, ptk7, twist1, sall4, th, ror2, twist1, and ptprq.[21]

Satellite Cells[edit]

The cells required to reconstitute the cells are stem cells or progenitor cells—cells capable of differentiating into the cells of the tail lost by autotomy or amputation. Satellite cells were identified in the Carolina Anole in 2017 by comparing the transcriptomes between lizard cells expressing the gene PAX7 (a known marker for muscle progenitor cells and the transcriptomes of mammalian satellite cells to demonstrate the similarities between the two populations of cells, indicating that these are likely the lizard’s resident population of progenitor cells that might be the key group of cells that divide to replace the lost tissue.[21]

Evolutionary Pressures[edit]

A lizard tail shed by autotomy
A lizard tail shed by autotomy

Many species of lizards benefit from the ability to sacrifice their tails in order to escape predators through a process called autotomy.[24][25] At the same time, the costs of losing a tail are numerous for a lizard, including reduced locomotion,[6][7] energetic costs,[26][27] loss of predator-evasion tools,[28] and lower social status.[29] These selective pressures have been demonstrated to correlate directly with tail anatomy and ecology in a diverse number of lizard species.[30] Consequently, the evolution of lizard tail regeneration is closely linked to the evolution of autotomy as an anti-predation survival strategy.

Although these two traits are closely correlated, they are independent from one another; lizard tail regeneration occurs in response to any sufficient tail injury regardless of whether autotomy occurs.[9][31] Furthermore, despite the lack of autotomic ability in recently regenerated tail, the regenerated tail is capable of re-regenerating after subsequent damage to its collagen structure.[4]

Lizard tail regeneration is not known to provoke a facultative metabolic increase.[25] This distinguishes lizard tail regeneration from most instances of regeneration in other animals, where regeneration tends to transiently increase metabolic function[32] and increased metabolic function tends to augment regenerative capacity.[33] Some evolutionary biologists see this as evidence that lizard tail regeneration and autotomy evolved together as phenotypically integrated traits.[34]

Fossils belonging to captorhinidae from the Early Permian era show intravertebral fracture planes,[35] a feature common to lizards capable of autotomy. These fossil records suggest that the evolution of autotomy, and by extension tail regeneration, occurred at least one other time in history in a species with an ostensibly similar ecological niche.

Abnormal Regeneration[edit]

Lizard tail bifurcation occurs when the a lizard's tail sustains enough damage to initiate caudal regeneration, but not enough to sever the original tail. It is remarkably common in specimens caught in the wild.[36] One specimen has even been observed with "a caudal hexafurcation",[37] or six tails, following abnormal regeneration.

The most common cause of tail bifurcation in the wild is a faulty or partial autotomy committed during a predator attack.[36] Partial autotomy and shallow caudal wounds can both cause damage to the lizard tail ependyma, which has been demonstrated to initiate lizard tail regeneration when damaged and result in additional tails.[36] Ependymal transplants have also been shown to induce ectopic tail growth.[20]

Potential Applications in Human Medicine[edit]

The end goal of regenerative medicine is widely considered to be complete human limb regeneration.[38] Unfortunately, the majority of vertebrate model organisms capable of limb regeneration are anamniotes or 'lower vertebrates', such as zebrafish and axolotl, whereas humans are amniotes or 'higher vertebrates'. Amniotes possess more complex immune systems and lower tissue water content when compared to anamniotes,[39] two barriers to true regeneration which encourage scarring and non-regenerative wound healing. As the only amniotes capable of functional limb regeneration, lizards are noteworthy regenerative models[15] precisely because the mechanisms behind lizard tail regeneration provide potential models for bypassing these barriers in human beings.

Research on lizard tail regeneration also focuses on comparisons between amphibian, mammalian, and reptilian models of regeneration. One study discovered genes that control cartilage formation to be active in lizard tail but not in mouse satellite cells.[40] Similar studies continue to identify and investigate potential genetic "switches", which could pave the way for regenerative therapies in human beings.

See Also[edit]

References[edit]

  1. ^ Goss, R. J.; Holt, Roger (1992). "Epimorphic vs. tissue regeneration in Xenopus forelimbs". The Journal of Experimental Zoology. 261 (4): 451–457. doi:10.1002/jez.1402610412. PMID 1569412.
  2. ^ Dent, J. N. (1962). "Limb regeneration in larvae and metamorphosing individuals of the South African clawed toad". Journal of Morphology. 110 (1): 61–77. doi:10.1002/jmor.1051100105. PMID 13885494.
  3. ^ a b Song, F.; Li, B.; Stocum, D. L. (2010). "Amphibians as research models for regenerative medicine". Organogenesis. 6 (3): 141–150. doi:10.4161/org.6.3.12039. PMID 21197215.
  4. ^ a b c d Barr, J. I. (2019). "Re-regeneration to reduce negative effects associated with tail loss in lizards". Scientific Reports. 9 (18717). doi:10.1038/s41598-019-55231-6.
  5. ^ Dugès, A. (1829). Mémoire sur les espèces indigènes du genre Lacerta.
  6. ^ a b Martin, J.; Avery, R. A. (1998). "Effects of Tail Loss on the Movement Patterns of the Lizard, Psammodromus algirus". Functional Ecology. 12 (5): 794–802. doi:10.1046/j.1365-2435.1998.00247.x.
  7. ^ a b Fleming, P. A.; Bateman, P. W. (2012). "Autotomy, Tail Regeneration and Jumping ability in Cape Dwarf Geckos (Lygodactylus capensis) (Gekkonidae)". African Zoology. 47 (1): 55–59. doi:10.3377/004.047.0110.
  8. ^ a b Lozito, T. P.; Tuan, R. S. (2015). "Lizard tail regeneration: Regulation of two distinct cartilage regions by Indian hedgehog". Developmental Biology. 399 (2): 249–262. doi:10.1016/j.ydbio.2014.12.036. PMID 25596336.
  9. ^ a b Lozito, T. P.; Tuan, R. S. (2016). "Lizard tail regeneration as an instructive model of enhanced healing capabilities in an adult amniote". Connective Tissue Research. 58 (2): 145–154. doi:10.1080/03008207.2016.1215444. PMID 27459585.
  10. ^ Hooker, D. (1912). Die Nerven im regenerieten Schwanz der Eidechsen. pp. 217–222.
  11. ^ a b c Simpson, S. B. (1970). "Studies on Regeneration of the Lizard's Tail". American Zoologist. 10 (2): 157–165. doi:10.1093/icb/10.2.157. PMID 5426257.
  12. ^ a b c Fisher, R. E.; Geiger, L. A.; Stroik, L. K. (2012). "A Histological Comparison of the Original and Regenerated Tail in the Green Anole, Anolis carolinensis". Anatomical Record. 295 (10): 1609–1619. doi:10.1002/ar.22537. PMID 22933242.
  13. ^ Rai, M. F.; Hashimoto, S.; Johnson, E. E. (2012). "Heritability of articular cartilage regeneration and its association with ear wound healing in mice". Arthritis and Rheumatism. 64 (7): 2300–2310. doi:10.1002/art.34396. PMID 22275233.
  14. ^ Schall, J. J.; Bromwich, C. R.; Werner, Y. L.; Midlege, J. (1989). "Clubbed Regenerated Tails in Agama agama and Their Possible Use in Social Interactions". Journal of Herpetology. 23 (3): 303–305. doi:10.2307/1564456.
  15. ^ a b c Gilbert, E. A. B.; Delorme, S. L.; Vickaryous, M. K. (2015). "The regeneration blastema of lizards: An amniote model for the study of appendage replacement". Regeneration. 2 (2): 45–53. doi:10.1002/reg2.31.
  16. ^ Singer, M.; Egloff, F. R. L. (1949). "The nervous system and regeneration of the forelimb of adult Triturus; the effect of limited nerve quantities on regeneration". The Journal of Experimental Zoology. 111 (2): 295–314. PMID 18141502.
  17. ^ Cox, P. G. (1969). "Some aspects of tail regeneration in the lizard, Anolis carolinensis. I. A description based on histology and autoradiography". The Journal of Experimental Zoology. 171 (2): 127–149. doi:10.1002/jez.1401710202.
  18. ^ Kamrin, R. P.; Singer, M. (1955). "The influence of the spinal cord in regeneration of the tail of the lizard, Anolis carolinensis". The Journal of Experimental Zoology. 128 (3): 611–627. doi:10.1002/jez.1401280314.
  19. ^ Economides, K. D.; Zeltser, Lori; Capecchi, M. R. (2003). "Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae". Developmental Biology. 256 (2): 317–330. PMID 12679105.
  20. ^ a b Simpson, S. B. (1964). "Analysis of tail regeneration in the lizard Lygosoma laterale. I. Initiation of regeneration and cartilage differentiation: The role of ependyma". Journal of Morphology. 114 (3): 425–435. doi:10.1002/jmor.1051140305. PMID 14165134.
  21. ^ a b c d e Hutchins, E. D.; Markov, G. J.; Eckalbar, W. L. (2014). "Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis reveals activation of conserved vertebrate developmental and repair mechanisms". PloS One. 9 (8): E105004. doi:10.1371/journal.pone.0105004. PMID 25140675.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ Products, National Research Council (US) Committee on Technological Options to Improve the Nutritional Attributes of Animal (1988). Hormonal Regulation of Growth. National Academies Press (US).
  23. ^ Tosenberger, A.; Bessonov, N.; Levin, M.; Reinberg, N.; Volpert, V.; Morozova, N. (2015). "A conceptual model of morphogenesis and regeneration". Acta biotheoretica. 63 (3): 283–294. doi:10.1007/s10441-015-9249-9. ISSN 0001-5342. PMC 4868547. PMID 25822060.
  24. ^ Kelehear, C.; Webb, J. K. (2006). "Effects of Tail Autotomy on Anti-predator Behavior and Locomotor Performance in a Nocturnal Gecko". Copeia. 2006 (4): 803–809. doi:10.1643/0045-8511(2006)6[803:EOTAOA]2.0.CO2.
  25. ^ a b Congdon, J. D.; Vitt, L. J.; King, W. W. (1974). "Geckos: Adaptive Significance and Energetics of Tail Autotomy". Science (American Association for the Advancement of Science). 184 (4144): 1379–1380. doi:10.1126/science.184.4144.1379. PMID 4833262.
  26. ^ Daniels, C. B. (1984). "The Importance of Caudal Lipid in the Gecko Phyllodactylus marmoratus". Herpetologica. 40 (3): 337–344. ISSN 0018-0831.
  27. ^ Avery, R. (1970). "Utilization of caudal fat by hibernating common lizards, Lacerta vivipara". Comparative Biochemistry and Physiology. 37 (1): 119–121. doi:10.1016/0010-406X(70)90965-5.
  28. ^ Rolek, R. W. (2014). "Bite me: Blue tails as a 'risky-decoy' defense tactic for lizards". Current Zoology. 60 (3): 333–337. doi:10.1093/czoolo/60.3.333.
  29. ^ Fox, S. F.; Heger, N. A.; Delay, L. S. (1990). "Social cost of tail loss in Uta stansburiana: Lizard tails as status-signalling badges". Animal Behaviour. 39 (3): 549–554. doi:10.1016/S0003-3472(05)80421-X.
  30. ^ Fleming, P. A.; Valentine, L. E.; Bateman, P. W. (2013). "Telling Tails: Selective Pressures Acting on Investment in Lizard Tails". Physiological and Biochemical Zoology. 86 (6): 645–658. doi:10.1086/673864. PMID 24241062.
  31. ^ Delorme, S. L.; Lungu, I. M.; Vickaryous, M. K. (2012). "Scar-Free Wound Healing and Regeneration Following Tail Loss in the Leopard Gecko, Eublepharis macularius". Anatomical Record. 295 (10): 1575–1595. doi:10.1002/ar.22490. PMID 22933425.
  32. ^ Brockes, J. P.; Kumar, A. (2008). "Comparative Aspects of Animal Regeneration". Annual Review of Cell and Developmental Biology. 24 (1): 525–549. doi:10.1146/annurev.cellbio.24.110707.175336. PMID 18598212.
  33. ^ Haoming, L.; Yingying, D. (2020). "Bioenergetic-active materials enhance tissue regeneration by modulating cellular metabolic state". Science Advances. 6 (13): Eaay7608. doi:10.1126/sciadv.aay7608. PMID 32232154.
  34. ^ {{cite journal | last1 = Arnold | first1 = E. | year = 2007 | title = Evolutionary aspects of tail shedding in lizards and their relatives | url = https://www.tandfonline.com/doi/abs/10.1080/00222938400770131 | journal = Journal of Natural History | volume = 18 | issue = 1 | pages = 127-169 | doi = 10.1080/00222938400770131
  35. ^ Leblanc, A. R. H.; MacDougall, M. J.; Haridy, Y.; Scott, D.; Reisz, R. R. (2018). "Caudal autotomy as anti-predatory behaviour in Palaeozoic reptiles". Scientific Reports. 8 (1): 3328–11. doi:10.1038/s41598-018-21526-3. PMID 29507301.
  36. ^ a b c Barr, J. I.; Somaweera, R.; Godfrey, S. S. (2020). "When one tail isn't enough: Abnormal caudal regeneration in lepidosaurs and its potential ecological impacts". Biological Reviews of the Cambridge Philosophical Society. 95 (5): 1479–1496. doi:10.1111/brv.12625.
  37. ^ Pelegrin, N.; Leão, S. M. (2016). "Injured Salvator merianae (Teiidae) regenerates six tails in central Argentina". Cuadernos De Herpetología. 30 (1): 21–23. ISSN 1852-5768.
  38. ^ Laurencin, C. T.; Nair, L. S. (2016). "The Quest toward limb regeneration: A regenerative engineering approach". Regenerative Biomaterials. 3 (2): 123–125. doi:10.1126/sciadv.aay7608. PMID 32232154.
  39. ^ Alibardi, L. (2017). "Hyaluronic acid in the tail and limb of amphibians and lizards recreates permissive embryonic conditions for regeneration due to its hygroscopic and immunosuppressive properties". Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution. 328 (8): 760–771. doi:10.1002/jez.b.22771. PMID 29106045.
  40. ^ Tokuyama, Minami A.; Xu, Cindy; Fisher, Rebecca E.; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M. (2018). "Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail". Developmental Biology. 433 (2): 287–296. doi:10.1016/j.ydbio.2017.10.003. ISSN 1095-564X. PMC 5764105. PMID 29291978.
Retrieved from "https://en.wikipedia.org/w/index.php?title=User:CMSRegenBio/sandbox&oldid=985549191"