Editing Axolotl (section)

==Description==
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A sexually mature adult axolotl, at age 18–27 months, ranges in length from {{convert|15| to |45|cm|0|abbr=on}}, although a size close to {{convert|23|cm|0|abbr=on}} is most common and greater than {{convert|30|cm|abbr=on}} is rare. Axolotls possess features typical of salamander larvae, including [[external gills]] and a caudal fin extending from behind the head to the vent.<ref>San Francisco Examiner (San Francisco, California) 7 August 1887, page 9, authored by [[Yda Addis]]</ref><ref>{{Citation|last1=McIndoe|first1=Rosemary|title=Functional morphology of gills in larval amphibians|date=1984|url=https://doi.org/10.1007/978-94-009-6536-2_4|work=Respiration and metabolism of embryonic vertebrates: Satellite Symposium of the 29th International Congress of Physiological Sciences, Sydney, Australia, 1983|pages=55–69|editor-last=Seymour|editor-first=Roger S.|series=Perspectives in vertebrate science|place=Dordrecht|publisher=Springer Netherlands|language=en|doi=10.1007/978-94-009-6536-2_4|isbn=978-94-009-6536-2|access-date=2021-05-13|last2=Smith|first2=D. G.}}</ref> External gills are usually lost when salamander species mature into adulthood, although the axolotl maintains this feature.<ref name=":1">{{Cite book|last=Kardong|first=Kenneth V|url=https://www.worldcat.org/oclc/1053847969|title=Vertebrates: comparative anatomy, function, evolution|date=2019|publisher=McGraw-Hill Education |isbn=978-1-259-70091-0|language=English|oclc=1053847969}}</ref> This is due to their neoteny, where axolotls are much more aquatic than other salamander species.<ref name=":5"/>
Their heads are wide, and their eyes are [[Eyelid|lidless]]. Their limbs are underdeveloped and possess long, thin digits. Three pairs of [[External gills|external gill stalks (rami)]] originate behind their heads and are used to move oxygenated water. The external gill rami are lined with filaments (fimbriae) to increase surface area for gas exchange.<ref name=":1" /> Four-gill slits lined with [[gill rakers]] are hidden underneath the external gills, which prevent food from entering and allow particles to filter through. Males can be identified by their swollen [[cloaca]]e lined with papillae, while females have noticeably wider bodies when [[Gravidity and parity|gravid]] and full of eggs. 
[[File:Buccal pumping.jpg|thumb|428x428px|Buccal pumping]]
Axolotls have barely visible [[Vestigiality|vestigial]] teeth, which develop during metamorphosis. The primary method of feeding is by [[suction feeding|suction]], during which their rakers interlock to close the gill slits. External gills are used for respiration, although [[buccal pumping]] (gulping air from the surface) may also be used to provide oxygen to their lungs.<ref name=":1" /> Buccal pumping can occur in a two-stroke manner that pumps air from the mouth to the lungs, and with four-stroke that reverses this pathway with compression forces.
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The [[wild type]] animal (the "natural" form) is brown or tan with gold speckles and an [[Olive (color)|olive]] undertone, and possess an ability to subtly alter their color by changing the relative size and thickness of their [[melanophore]]s, presumably for [[camouflage]].<ref>{{Cite journal |last1=Pietsch |first1=Paul |last2=Schneider |first2=Carl W. |date=1985 |title=Vision and the skin camouflage reactions of ''Ambystoma'' larvae: the effects of eye transplants and brain lesions |journal=Brain Research |volume=340 |issue=1 |pages=37–60 |doi=10.1016/0006-8993(85)90772-3|pmid=4027646 |s2cid=22723238 }}</ref> 
Axolotls have four pigmentation genes; when mutated, they create different color variants.{{Citation needed|date=May 2025}} The five most common mutant colors are listed below;{{Clarify|reason=There are four color morphs listed|date=May 2025}}

# [[Leucistic]]: pale pink with black eyes.
# [[Xanthochromism|Xanthic]]: grey, with black eyes.
# [[Albinism]]: pale pink or white, with red eyes.
# [[Melanism]]: all black or dark blue with no gold speckling or olive tone.

In addition, there is wide individual variability in the size, frequency, and intensity of the gold speckling, and at least one variant develops a black and white [[piebald]] appearance upon reaching maturity.<ref>{{Cite web|url=https://exopetguides.com/axolotl/axolotl-colors/|title=18 Types of Axolotl Colors You Can Own (Axolotl Color Guide)|date=August 14, 2019}}</ref> Because [[Breeder|pet breeders]] frequently [[Crossbreed|cross]] the variant colors, double [[homozygous]] mutants are common in the [[pet trade]], especially white/pink animals with pink eyes that are double homozygous mutants for both the albino and leucistic genes.<ref name="Color Atlas of Pigment Genes">{{Cite journal |last1=Frost |first1=Sally K. |last2=Briggs |first2=Fran |last3=Malacinski |first3=George M. |date=1984 |title=A color atlas of pigment genes in the Mexican axolotl (''Ambystoma mexicanum'') |journal=Differentiation |volume=26 |issue=1–3 |pages=182–188 |doi=10.1111/j.1432-0436.1984.tb01393.x}}</ref> 
[[File:Cromatóforos de larva de axolote pardo (Ambystoma mexicanum).jpg|thumb|Melanophores of a larva axolotl]]
The 32 billion [[base pair]] long sequence of the axolotl's [[genome]] was published in 2018 and was the largest animal genome completed at the time. It revealed species-specific [[genetic pathway]]s that may be responsible for limb regeneration.<ref name=":0">{{Cite journal |last1=Nowoshilow |first1=Sergej |last2=Schloissnig |first2=Siegfried |last3=Fei |first3=Ji-Feng |last4=Dahl |first4=Andreas |last5=Pang |first5=Andy W. C. |last6=Pippel |first6=Martin |last7=Winkler |first7=Sylke |last8=Hastie |first8=Alex R. |last9=Young |first9=George |date=2018-01-24 |title=The axolotl genome and the evolution of key tissue formation regulators |journal=[[Nature (journal)|Nature]] |volume=554 |issue=7690 |pages=50–55 |doi=10.1038/nature25458 |pmid=29364872 |issn=1476-4687 |bibcode=2018Natur.554...50N |doi-access=free |hdl=21.11116/0000-0003-F659-4 |hdl-access=free }}</ref> Although the axolotl genome is about 10 times as large as the [[human genome]], it encodes a similar number of proteins, namely 23,251<ref name=":0" /> (the human genome encodes about 20,000 proteins). The size difference is mostly explained by a large fraction of [[repeated sequence (DNA)|repetitive sequences]], but such repeated elements also contribute to increased median [[intron]] sizes (22,759&nbsp;bp) which are 13, 16 and 25 times that observed in human (1,750&nbsp;bp), [[mouse]] (1,469&nbsp;bp) and [[Nanorana parkeri|Tibetan frog]] (906&nbsp;bp), respectively.<ref name=":0" />

===Physiology===
==== Regeneration ====
The feature of the axolotl that attracts most attention is its healing ability: the axolotl does not heal by [[scar]]ring, but is capable of [[regeneration (biology)|tissue regeneration]]; entire lost appendages such as limbs and the tail are regrow over a period of months, and, in certain cases, more vital structures, such as the tissues of the eye and [[heart]] can be regrown.<ref name="nickbaker">{{cite video |date= 2009-11-11 |title= Weird Creatures with Nick Baker |medium= Television series |publisher= [[The Science Channel]] |location= Dartmoor, England, UK <!--|access-date= 2009-12-04 -->|time= 00:25}}</ref><ref>{{Cite journal|last1=Caballero-Pérez|first1=Juan|last2=Espinal-Centeno| first2= Annie|last3=Falcon|first3=Francisco|last4=García-Ortega|first4=Luis F.|last5=Curiel-Quesada|first5=Everardo|last6=Cruz-Hernández| first6= Andrés| last7=Bako|first7=Laszlo|last8=Chen|first8=Xuemei|last9=Martínez|first9=Octavio|last10=Alberto Arteaga-Vázquez| first10= Mario| last11= Herrera-Estrella|first11=Luis|date=January 2018|title=Transcriptional landscapes of Axolotl (Ambystoma mexicanum)|journal= [[Developmental Biology]]| language= en| volume=433|issue=2|pages=227–239|doi=10.1016/j.ydbio.2017.08.022|pmid=29291975|doi-access=}}</ref> They can restore parts of their [[central nervous system]], such as less vital parts of their brains. They can also readily accept [[Organ transplantation|transplants]] from other individuals, including eyes and parts of the brain—restoring these alien organs to full functionality. In some cases, axolotls have been known to repair a damaged limb, as well as regenerating an additional one, ending up with an extra appendage that makes them attractive to pet owners as a [[novelty]]. Their ability to regenerate declines with age but does not disappear, though in metamorphosed individuals, the ability to regenerate is greatly diminished. Axolotls experience [[indeterminate growth]], their bodies continuing to grow throughout their life, and some consider this trait to be a direct contributor to their regenerative abilities.<ref>{{Cite journal |last=Sandoval-Guzmán |first=Tatiana |date=August 2023 |title=The axolotl |url=https://www.nature.com/articles/s41592-023-01961-5 |journal=Nature Methods |language=en |volume=20 |issue=8 |pages=1117–1119 |doi=10.1038/s41592-023-01961-5 |pmid=37553398 |s2cid=260699417 |issn=1548-7091}}</ref> The axolotl is therefore used as a model for the development of limbs in vertebrates.<ref name=PMID18814845>{{cite journal |last1=Roy |first1=S |last2=Gatien |first2=S |title=Regeneration in axolotls: a model to aim for! |journal= [[Experimental Gerontology]] |date=November 2008 |volume=43 |issue=11 |pages=968–73 |pmid=18814845 |doi=10.1016/j.exger.2008.09.003 |s2cid=31199048 }}</ref> There are three basic requirements for regeneration of the limb: the wound [[epithelium]], nerve signaling, and the presence of cells from the different limb axes.<ref>{{cite journal |last1=Vieira |first1=Warren A. |last2=Wells |first2=Kaylee M. |last3=McCusker |first3=Catherine D. |title=Advancements to the Axolotl Model for Regeneration and Aging |journal=Gerontology |date=2020 |volume=66 |issue=3 |pages=212–222 |doi=10.1159/000504294 |pmid=31779024|pmc=7214127 |doi-access=free}}</ref> A wound epidermis is quickly formed by the cells to cover up the site of the wound. In the following days, the cells of the wound epidermis divide and grow, quickly forming a [[blastema]], which means the wound is ready to heal and undergo patterning to form the new limb.

It is believed that during limb generation, axolotls have a different system to regulate their internal [[macrophage]] level and suppress [[inflammation]], as scarring prevents proper healing and regeneration.<ref>{{cite journal |last1=Goodwin |first1=James W. |last2=Pinto |first2= Alexander R. |last3=Rosenthal |first3=Nadia A. |editor-first= Eric N.| editor-last= Olson |title=Macrophages are required for adult salamander limb regeneration |journal= [[Proceedings of the National Academy of Sciences of the United States of America]]|date=June 4, 2013 |volume=110 |issue=23 |pages=9415–9420 |doi=10.1073/pnas.1300290110 |pmid=23690624 |pmc=3677454 |bibcode=2013PNAS..110.9415G |doi-access=free }}</ref> However, this belief has been questioned by other studies.<ref>{{cite journal |last1=Pedersen |first1=Katherine |last2=Rasmussen |first2=Rikke Kongsgaard |last3=Dittrich |first3=Anita |last4=Pedersen |first4= Michael |last5=Lauridsen |first5=Henrik |title=Modulating the immune response and the pericardial environment with LPS or prednisolone in the axolotl does not change the regenerative capacity of cryoinjured hearts |journal=[[The FASEB Journal]] |date=April 17, 2020 |volume=34 |issue= S1 |page=1 |doi=10.1096/fasebj.2020.34.s1.04015 |s2cid=218792957 |doi-access=free }}</ref> The axolotl's regenerative properties leave the species as the perfect model to study the process of [[stem cell]]s and its own neoteny feature. Current research can record specific examples of these regenerative properties through tracking cell fates and behaviors, lineage tracing skin [[triploid]] cell [[Graft (surgery)|grafts]], pigmentation imaging, [[electroporation]], tissue clearing and lineage tracing from dye labeling. The newer technologies of [[germline modification]] and [[transgenesis]] are better suited for live imaging the regenerative processes that occur for axolotls.<ref>Masselink, Wouter, and Elly M. Tanaka. "Toward Whole Tissue Imaging of Axolotl Regeneration." Developmental Dynamics, vol. 250, no. 6, 2020, pp. 800–806., https://doi.org/10.1002/dvdy.282.</ref>

==== Neoteny ====
{{Main|Neoteny}}
<!-- This is the sort of stuff that gets put in a box in fancy journal articles. -->
{{Side box|metadata=no||text='''Role of iodine'''
In animals with functioning thyroid glands, iodine in the form of iodide is selectively gathered into the colloid of the thyroid. Inside the colloid, iodide is reduced to elemental iodine (I<sub>2</sub>), which reacts with the [[tyrosyl]] residues of [[thyroglobulin]]. Two iodinated tyrosyl residues are conjugated together. When they are cleaved from the thyroglobulin chain, thyroid hormone is obtained.<ref name=boron2012>Chapter 49, "Synthesis of Thyroid Hormones" in: {{cite book |author1=Walter F. Boron |author2=Emile L. Boulpaep |title=Medical Physiology |edition= 2nd|publisher=Elsevier/Saunders |year=2012 |isbn=9781437717532}}{{page needed|date=April 2016}}</ref>

[[Diiodotyrosine]], an analogue of the iodinated [[thyroglobulin]] precursor in thyroxine biosynthesis, causes metamorphosis in axolotls that have their thyroids removed.<ref>{{cite journal |last1=Swingle |first1=W. W. |title=Iodine and Amphibian Metamorphosis |journal=The Biological Bulletin |date=November 1923 |volume=45 |issue=5 |pages=229–253 |doi=10.2307/1536749|jstor=1536749 }}</ref> [[Lugol's solution]], which contains both iodide and I<sub>2</sub>, triggers metamorphosis when injected.<ref>{{cite journal |last1=Ingram |first1=W. R. |title=Metamorphosis of the Colorado Axolotl by Injection of Inorganic Iodine. |journal=Experimental Biology and Medicine |date=1 December 1928 |volume=26 |issue=3 |pages=191 |doi=10.3181/00379727-26-4212}}</ref> This is because diiodotyrosine and thyroxine is produced when I<sub>2</sub> reacts with proteins other than thyroglobulin. If given in a bath instead of injected, I<sub>2</sub> has no effect on axolotls.<ref>{{cite journal |last1=Dvoskin |first1=Samuel |title=The Thyroxine-Like Action of Elemental Iodine in the Rat and Chick1 |journal=Endocrinology |date=May 1947 |volume=40 |issue=5 |pages=334–352 |doi=10.1210/endo-40-5-334|pmid=20245954 }}</ref> [[Iodide]], which does not react with proteins, does not trigger metamorphosis. It does speed up the rate of metamorphosis, once it has been triggered by thyroid hormone extract.<ref>{{cite journal |last1=Krylov |first1=O. A. |title=The role of haloids (bromine and iodine) in the metamorphosis of amphibia |journal=Bulletin of Experimental Biology and Medicine |date=January 1961 |volume=50 |issue=1 |pages=724–727 |doi=10.1007/BF00796048}}</ref>
}}
Most amphibians begin their lives as [[aquatic animal]]s which are unable to live on dry land, often being dubbed as [[tadpole]]s. To reach [[adult]]hood, they go through a process called [[metamorphosis (biology)|metamorphosis]], in which they lose their gills and start living on land. The axolotl is unusual in that it has a lack of [[thyroid-stimulating hormone]], which is needed for the [[thyroid]] to produce [[thyroxine]] in order for the axolotl to go through metamorphosis; it keeps its gills and lives in water all its life, even after it becomes an adult and is [[sexual maturity|able to reproduce]]. Neoteny is the term for reaching sexual maturity without undergoing metamorphosis.<ref name="ley196802">{{Cite magazine |last=Ley
 |first=Willy |date=February 1968 |title=Epitaph for a Lonely Olm |department=For Your Information|url=https://archive.org/stream/Galaxy_v26n03_1968-02_modified#page/n37/mode/2up |magazine=Galaxy Science Fiction |pages=95–104}}</ref>

The genes responsible for neoteny in laboratory axolotls may have been identified; they are not linked to the genes of wild populations, suggesting [[artificial selection]] is the cause of complete neoteny in laboratory and pet axolotls.<ref name=":3">{{Cite journal|last=Malacinski |first=George M.|date=1978-05-01|title=The Mexican Axolotl, ''Ambystoma mexicanum'': Its Biology and Developmental Genetics, and Its Autonomous Cell-lethal Genes|journal=American Zoologist|volume=18|issue=2|pages=195–206|doi=10.1093/icb/18.2.195 |doi-access=free}}</ref> The genes responsible have been narrowed down to a small chromosomal region called ''met1'', which contains several candidate genes.<ref name=Crowner>{{cite journal |last1=Crowner |first1=Anne |last2=Khatri |first2=Shivam |last3=Blichmann |first3=Dana |last4=Voss |first4=S. Randal |title=Rediscovering the Axolotl as a Model for Thyroid Hormone Dependent Development |journal=Frontiers in Endocrinology |date=12 April 2019 |volume=10 |page=237 |doi=10.3389/fendo.2019.00237 |doi-access=free|pmid=31031711 |pmc=6473073 }}</ref>

Many other species within the axolotl's genus are also either entirely neotenic or have neotenic populations. [[Siren (amphibian)|Siren]]s, ''[[Necturus]]'' mudpuppies, and the troglobytic [[olm]] are other examples of neotenic salamanders, although unlike axolotls, they cannot be induced to metamorphose by an injection of iodine or thyroxine hormone.

Neoteny has been observed in all [[salamander]] families in which it seems to be a survival mechanism, in aquatic environments only of mountain and hill, with little food and, in particular, with little iodine. In this way, salamanders can reproduce and survive in the form of a smaller larval stage, which is aquatic and requires a lower quality and quantity of food compared to the big adult, which is terrestrial. If the salamander larvae ingest a sufficient amount of iodine, directly or indirectly through [[cannibalism]], they quickly begin metamorphosis and transform into bigger terrestrial adults, with higher dietary requirements, but an ability to disperse across dry land.<ref>{{cite web|last=Venturi|first= S.|year=2004 |url= https://sites.google.com/site/iodinestudies/morosini |archive-date=4 March 2017 |url-status = dead|archive-url=https://web.archive.org/web/20170304010444/https://sites.google.com/site/iodinestudies/morosini|access-date = 25 September 2020|title= Iodine and Evolution. DIMI-Marche}}</ref> In fact, in some high mountain lakes there live dwarf forms of [[salmonids]] that are caused by deficiencies in food and, in particular, iodine, which causes [[cretinism]] and [[dwarfism]] due to [[hypothyroidism]], as it does in humans.

==== Metamorphosis ====
The axolotl's body has the capacity to go through metamorphosis if given the necessary hormone, but axolotls do not produce it, and must obtain it from an external source, after which an axolotl undergoes an induced metamorphosis and begins living on land.<ref>{{Cite journal |last1=Demircan |first1=Turan |last2=Ovezmyradov |first2=Guvanch |last3=Yıldırım |first3=Berna |last4=Keskin |first4=İlknur |last5=İlhan |first5=Ayşe Elif |last6=Fesçioğlu |first6=Ece Cana |last7=Öztürk |first7=Gürkan |last8=Yıldırım |first8=Süleyman |date=2018-07-20 |title=Experimentally induced metamorphosis in highly regenerative axolotl (''Ambystoma mexicanum'') under constant diet restructures microbiota |journal=Scientific Reports |language=en |volume=8 |issue=1 |page=10974 |doi=10.1038/s41598-018-29373-y |pmid=30030457 |pmc=6054665 |bibcode=2018NatSR...810974D }}</ref> Research on this phenomenon has been performed for over a century; in modern laboratory conditions, metamorphosis is reliably induced by administering either the thyroid hormone [[thyroxine]] or a [[thyroid-stimulating hormone]]. The former is more commonly used.<ref name=Crowner/>
[[File:Ambystomas.jpg|thumb|Metamorphosed axolotls]]
In the absence of induced metamorphosis, larval axolotls start absorbing iodide into their thyroid glands at 30 days post-fertilization. Larval axolotls do produce thyroid hormone from iodide, but the amount appears highly variable. Adult axolotls do not produce thyroid hormone unless metamorphism is triggered.<ref name="pmid9371791">{{cite journal |last1=Brown |first1=Donald D. |title=The role of thyroid hormone in zebrafish and axolotl development |journal=Proceedings of the National Academy of Sciences |date=25 November 1997 |volume=94 |issue=24 |pages=13011–13016 |doi=10.1073/pnas.94.24.13011 |doi-access=free |pmid=9371791 |pmc=24254|bibcode=1997PNAS...9413011B }}</ref>

An axolotl undergoing metamorphosis experiences a number of physiological changes that help them adapt to life on land. These include increased muscle tone in limbs, the absorption of gills and fins into the body, the development of eyelids, and a reduction in the skin's permeability to water, allowing the axolotl to stay more easily hydrated when on land. The lungs of an axolotl, though present alongside gills after reaching non-metamorphosed adulthood, develop further during metamorphosis.<ref name=":6">{{Cite web|title=Axolotls - Metamorphosed & Tiger Salamanders|url=https://www.axolotl.org/tiger_salamander.htm|access-date=2022-01-25|website=www.axolotl.org}}</ref> Axolotl that complete their metamorphosis resembles an adult [[plateau tiger salamander]], though the axolotl differs in its longer toes.{{Citation needed|date=February 2011}}