View source for Xenopus

{{Short description|Genus of amphibians}}
{{Automatic taxobox
| oldest_fossil = Oligocene
| image = Xenopus laevis.jpg
| image_caption = ''[[Xenopus laevis]]''
| taxon = Xenopus
| authority = [[Johann Georg Wagler|Wagler]] 1827
| subdivision_ranks = Species
| subdivision = [[#Species|See text]]
}}

'''''Xenopus''''' ({{IPAc-en|ˈ|z|ɛ|n|ə|p|ə|s}}{{refn|{{Cite encyclopedia |url=http://www.lexico.com/definition/Xenopus |archive-url=https://web.archive.org/web/20200322182228/https://www.lexico.com/definition/xenopus |archive-date=2020-03-22 |title=Xenopus |dictionary=[[Lexico]] UK English Dictionary |publisher=[[Oxford University Press]]}} }}{{refn|{{MerriamWebsterDictionary|access-date=2016-01-21|Xenopus}}}}) (Gk., ξενος, ''xenos''&nbsp;=&nbsp;strange, πους, ''pous''&nbsp;=&nbsp;foot, commonly known as the '''clawed frog''') is a [[genus]] of highly aquatic [[frogs]] native to [[sub-Saharan Africa]].  Twenty species are currently described within it. The two best-known species of this genus are ''[[Xenopus laevis]]'' and ''[[Xenopus tropicalis]]'', which are commonly studied as [[model organism]]s for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects.<ref>{{cite journal | vauthors = Nenni MJ, Fisher ME, James-Zorn C, Pells TJ, Ponferrada V, Chu S, Fortriede JD, Burns KA, Wang Y, Lotay VS, Wang DZ, Segerdell E, Chaturvedi P, Karimi K, Vize PD, Zorn AM | display-authors = 6 | title = Xenbase: Facilitating the Use of ''Xenopus'' to Model Human Disease | journal = Frontiers in Physiology | volume = 10 | page = 154 | year = 2019 | pmid = 30863320 | pmc = 6399412 | doi = 10.3389/fphys.2019.00154 | doi-access = free }}</ref><ref name="wallingford">{{cite journal | vauthors = Wallingford JB, Liu KJ, Zheng Y | title = Xenopus | journal = Current Biology | volume = 20 | issue = 6 | pages = R263–R264 | date = March 2010 | pmid = 20334828 | doi = 10.1016/j.cub.2010.01.012 | doi-access = free | bibcode = 2010CBio...20.R263W }}</ref><ref name="Harland">{{cite journal | vauthors = Harland RM, Grainger RM | title = Xenopus research: metamorphosed by genetics and genomics | journal = Trends in Genetics | volume = 27 | issue = 12 | pages = 507–515 | date = December 2011 | pmid = 21963197 | pmc = 3601910 | doi = 10.1016/j.tig.2011.08.003 }}</ref>

The genus is also known for its [[polyploid]]y, with some species having up to 12 sets of [[chromosome]]s.

==Characteristics==

''Xenopus laevis'' is a rather inactive creature. It is incredibly hearty and can live up to 15 years. At times the ponds that ''Xenopus laevis'' is found in dry up, compelling it, in the dry season, to burrow into the mud, leaving a tunnel for air. It may lie dormant for up to a year. If the pond dries up in the rainy season, ''Xenopus laevis'' may migrate long distances to another pond, maintaining hydration by the rains. It is an adept swimmer, swimming in all directions with ease. It is barely able to hop, but it is able to crawl. It spends most of its time underwater and comes to surface to breathe. Respiration is predominantly through its well-developed lungs; there is little cutaneous respiration.

===Description===

All species of ''Xenopus'' have flattened, somewhat egg-shaped and streamlined bodies, and very slippery skin (because of a protective mucus covering).<ref name="arizona">{{cite web|url=http://www.iacuc.arizona.edu/training/xenopus/intro.html|title=IACUC Learning Module — ''Xenopus laevis''|publisher=University of Arizona|access-date=2009-10-11|archive-date=2010-06-26|archive-url=https://web.archive.org/web/20100626190703/http://www.iacuc.arizona.edu/training/xenopus/intro.html}}</ref> The frog's skin is smooth, but with a [[lateral line]] sensory organ that has a stitch-like appearance. The frogs are all excellent swimmers and have powerful, fully webbed toes, though the fingers lack webbing. Three of the toes on each foot have conspicuous black [[claw]]s.
	 
The frog's eyes are on top of the head, looking upwards. The [[pupils]] are circular. They have no moveable [[eyelids]], [[tongue]]s (rather it is completely attached to the floor of the mouth<ref name="arizona"/>) or [[eardrum]]s (similarly to [[Common Suriname toad|''Pipa pipa'', the common Suriname toad]]<ref name="noc-ani">{{cite book| vauthors = Roots C  |title=Nocturnal animals |publisher=Greenwood Press |page=19 |isbn=978-0-313-33546-4|year=2006}}</ref>).<ref name="passmore">{{cite book | vauthors = Passmore NI, Carruthers VC | date = 1979 | title = South African Frogs | pages = 42–43 | publisher = Witwatersrand University Press | location = Johannesburg | isbn = 0-85494-525-3 }}</ref>
	 
Unlike most amphibians, they have no [[haptoglobin]] in their [[blood]].<ref name="passmore"/>

===Behaviour===
''Xenopus'' species are entirely [[Aquatic animal|aquatic]], though they have been observed migrating on land to nearby bodies of water during times of [[drought]] or in heavy rain. They are usually found in [[lake]]s, [[river]]s, [[swamps]], potholes in streams, and man-made reservoirs.<ref name="passmore"/>

Adult frogs are usually both [[predator]]s and [[scavengers]], and since their tongues are unusable, the frogs use their small fore limbs to aid in the feeding process. Since they also lack [[vocal sac]]s, they make clicks (brief pulses of sound) underwater (again similar to ''[[Pipa pipa]]'').<ref name="noc-ani"/> Males establish a hierarchy of social dominance in which primarily one male has the right to make the advertisement call.<ref name="tobias-compet">{{cite journal | vauthors = Tobias ML, Corke A, Korsh J, Yin D, Kelley DB | title = Vocal competition in male Xenopus laevis frogs | journal = Behavioral Ecology and Sociobiology | volume = 64 | issue = 11 | pages = 1791–1803 | date = November 2010 | pmid = 21442049 | pmc = 3064475 | doi = 10.1007/s00265-010-0991-3 }}</ref> The females of many species produce a release call, and ''[[Xenopus laevis]]'' females produce an additional call when sexually receptive and soon to lay eggs.<ref name="tobias-rap">{{cite journal | vauthors = Tobias ML, Viswanathan SS, Kelley DB | title = Rapping, a female receptive call, initiates male-female duets in the South African clawed frog | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 4 | pages = 1870–1875 | date = February 1998 | pmid = 9465109 | pmc = 19205 | doi = 10.1073/pnas.95.4.1870 | doi-access = free | bibcode = 1998PNAS...95.1870T }}</ref> The ''Xenopus'' species are also active during the twilight (or [[crepuscular]]) hours.<ref name="passmore"/>

During breeding season, the males develop ridge-like nuptial pads (black in color) on their fingers to aid in grasping the female. The frogs' mating embrace is inguinal, meaning the male grasps the female around her waist.<ref name="passmore"/>

== Species ==
[[File:Xenopus laevis female with egg batch and Xenopus tropicalis male - journal.pbio.1001201.g001.png|thumb|A ''Xenopus laevis'' female with a batch of freshly laid eggs and a ''Xenopus tropicalis'' male]]

=== Extant species ===
{{Div col|colwidth=30em}}
*''[[Xenopus allofraseri]]''
*''[[Xenopus amieti]]'' ([[volcano clawed frog]])
*''[[Xenopus andrei]]'' ([[Andre's clawed frog]])
*''[[Xenopus borealis]]'' ([[Marsabit clawed frog]])
*''[[Xenopus boumbaensis]]'' ([[Mawa clawed frog]])
*''[[Xenopus calcaratus]]''
*''[[Xenopus clivii]]'' ([[Eritrea clawed frog]])
*''[[Xenopus epitropicalis]]'' ([[Cameroon clawed frog]])
*''[[Xenopus eysoole]]''
*''[[Xenopus fischbergi]]''
*''[[Xenopus fraseri]]'' ([[Fraser's platanna]])
*''[[Xenopus gilli]]'' ([[Cape platanna]])
*''[[Xenopus itombwensis]]''
*''[[Xenopus kobeli]]''
*''[[Xenopus laevis]]'' ([[African clawed frog]] or common platanna)
*''[[Xenopus largeni]]'' ([[Largen's clawed frog]])
*''[[Xenopus lenduensis]]'' ([[Lendu Plateau clawed frog]])
*''[[Xenopus longipes]]'' ([[Lake Oku clawed frog]])
*''[[Xenopus mellotropicalis]]''
*''[[Xenopus muelleri]]'' ([[Müller's platanna]])
*''[[Xenopus parafraseri]]''
*''[[Xenopus petersii]]'' ([[Peters' platanna]])
*''[[Xenopus poweri]]''
*''[[Xenopus pygmaeus]]'' ([[Bouchia clawed frog]])
*''[[Xenopus ruwenzoriensis]]'' ([[Uganda clawed frog]])
*''[[Xenopus tropicalis]]'' ([[western clawed frog]])
*''[[Xenopus vestitus]]'' ([[Kivu clawed frog]])
*''[[Xenopus victorianus]]'' ([[Lake Victoria clawed frog]])
*''[[Xenopus wittei]]'' ([[De Witte's clawed frog]])
{{Div col end}}

=== Fossil species ===
The following fossil species have been described:<ref name=FXenopus>[ ''Xenopus''] at [[Fossilworks]].org</ref>
* †''[[Xenopus arabiensis]]'' {{small|Henrici and Báez 2001}} - [[Oligocene]] [[Yemen Volcanic Group]], Yemen
* †''[[Xenopus hasaunus]]'' {{small|Spinar 1980}}
* †''[[Xenopus romeri]]'' {{small|Estes 1975}} - [[Itaboraian]] [[Itaboraí Formation]], Brazil
* †''[[Xenopus stromeri]]'' {{small|Ahl 1926}}
* ''cf. Xenopus sp.'' - [[Campanian]] - [[Los Alamitos Formation]], Argentina
* ''Xenopus (Xenopus) sp.'' - [[Late Oligocene]] [[Nsungwe Formation]], Tanzania
* ''Xenopus sp.'' - [[Miocene]] Morocco
* ''Xenopus sp.'' - [[Early Pleistocene]] [[Olduvai Formation]], Tanzania

== Model organism for biological research ==
Like many other [[frogs]], they are often used in laboratory as research subjects.<ref name="arizona"/> ''Xenopus'' embryos and eggs are a popular model system for a wide variety of biological studies.<ref name="wallingford"/><ref name="Harland"/>  This animal is used because of its powerful combination of experimental tractability and close evolutionary relationship with humans, at least compared to many model organisms.<ref name="wallingford"/><ref name="Harland"/>

''Xenopus'' has long been an important tool for ''in vivo studies'' in molecular, cell, and developmental biology of vertebrate animals.<ref name="Harland"/>  However, the wide breadth of ''Xenopus'' research stems from the additional fact that [[cell-free system|cell-free extracts]] made from ''Xenopus'' are a premier ''in vitro ''system for studies of fundamental aspects of cell and molecular biology.  Thus, ''Xenopus'' is a vertebrate model system that allows for high-throughput ''in vivo'' analyses of gene function and high-throughput biochemistry.  Furthermore, ''Xenopus'' oocytes are a leading system for studies of ion transport and channel physiology.<ref name="wallingford"/> ''Xenopus'' is also a unique system for analyses of genome evolution and whole genome duplication in vertebrates,<ref>{{cite journal | vauthors = Session AM, Uno Y, Kwon T, Chapman JA, Toyoda A, Takahashi S, Fukui A, Hikosaka A, Suzuki A, Kondo M, van Heeringen SJ, Quigley I, Heinz S, Ogino H, Ochi H, Hellsten U, Lyons JB, Simakov O, Putnam N, Stites J, Kuroki Y, Tanaka T, Michiue T, Watanabe M, Bogdanovic O, Lister R, Georgiou G, Paranjpe SS, van Kruijsbergen I, Shu S, Carlson J, Kinoshita T, Ohta Y, Mawaribuchi S, Jenkins J, Grimwood J, Schmutz J, Mitros T, Mozaffari SV, Suzuki Y, Haramoto Y, Yamamoto TS, Takagi C, Heald R, Miller K, Haudenschild C, Kitzman J, Nakayama T, Izutsu Y, Robert J, Fortriede J, Burns K, Lotay V, Karimi K, Yasuoka Y, Dichmann DS, Flajnik MF, Houston DW, Shendure J, DuPasquier L, Vize PD, Zorn AM, Ito M, Marcotte EM, Wallingford JB, Ito Y, Asashima M, Ueno N, Matsuda Y, Veenstra GJ, Fujiyama A, Harland RM, Taira M, Rokhsar DS | display-authors = 6 | title = Genome evolution in the allotetraploid frog Xenopus laevis | journal = Nature | volume = 538 | issue = 7625 | pages = 336–343 | date = October 2016 | pmid = 27762356 | pmc = 5313049 | doi = 10.1038/nature19840 | bibcode = 2016Natur.538..336S }}</ref> as different ''Xenopus'' species form a [[ploidy]] series formed by [[Hybrid (biology)|interspecific hybridization]].<ref>{{cite journal | vauthors = Schmid M, Evans BJ, Bogart JP | title = Polyploidy in Amphibia | journal = Cytogenetic and Genome Research | volume = 145 | issue = 3–4 | pages = 315–330 | date = 2015 | pmid = 26112701 | doi = 10.1159/000431388 | doi-access = free }}</ref>

In 1931, [[Lancelot Hogben]] noted that ''Xenopus laevis'' females ovulated when injected with the urine of pregnant women.<ref>{{cite journal | vauthors = Hogben L, Charles E, Slome D | title = Studies on the pituitary. 8. The relation of the pituitary gland to calcium metabolism and ovarian function in Xenopus. | journal = Journal of Experimental Biology | date = 1931 | volume = 8 | pages = 345–54 | url = http://jeb.biologists.org/content/8/4/345 | doi = 10.1242/jeb.8.4.345 | url-access = subscription | archive-date = 2018-08-13 | access-date = 2018-08-12 | archive-url = https://web.archive.org/web/20180813005317/http://jeb.biologists.org/content/8/4/345 | url-status = live }}</ref> This led to a pregnancy test that was later refined by South African researchers [[Hillel Abbe Shapiro]] and Harry Zwarenstein.<ref name="pmid20781969">{{cite journal | vauthors = Elkan ER | title = The Xenopus Pregnancy Test | journal = British Medical Journal | volume = 2 | issue = 4067 | pages = 1253–1274.2 | date = December 1938 | pmid = 20781969 | pmc = 2211252 | doi = 10.1136/bmj.2.4067.1253 }}</ref> A female Xenopus frog injected with a woman's urine was put in a jar with a little water. If eggs were in the water a day later it meant the woman was pregnant. Four years after the first ''Xenopus'' test, Zwarenstein's colleague, Dr Louis Bosman, reported that the test was accurate in more than 99% of cases.<ref>[https://www.bmj.com/content/2/4009/939.1|Early Diagnosis of Pregnancy]{{Dead link|date=July 2025 |bot=InternetArchiveBot |fix-attempted=yes }}, Louis P. Bosman, British Medical Journal 1937;2:939, 6 November 1937</ref> From the 1930s to the 1950s, thousands of frogs were exported across the world for use in these pregnancy tests.<ref>{{cite magazine|url=https://www.smithsonianmag.com/smart-news/doctors-used-to-use-live-african-frogs-as-pregnancy-tests-64279275/|title=Doctors Used to Use Live African Frogs As Pregnancy Tests|vauthors=Nuwer R|author-link=Rachel Nuwer|magazine=[[Smithsonian Magazine|Smithsonian.com]]|date=16 May 2013|access-date=30 October 2018|archive-date=16 November 2018|archive-url=https://web.archive.org/web/20181116041532/https://www.smithsonianmag.com/smart-news/doctors-used-to-use-live-african-frogs-as-pregnancy-tests-64279275/|url-status=live}}</ref>

The {{visible anchor|National Xenopus Resource|lc=National ''Xenopus'' Resource}} of the [[Marine Biological Laboratory]] is an ''in vivo'' repository for transgenic and mutant strains and a training center.<ref name="Marine Biological Laboratory">{{cite web | title=The National Xenopus Resource | website=Marine Biological Laboratory | url=https://www.mbl.edu/research/resources-research-facilities/national-xenopus-resource | access-date=2022-04-05 | archive-date=2022-04-04 | archive-url=https://web.archive.org/web/20220404193130/https://www.mbl.edu/research/resources-research-facilities/national-xenopus-resource | url-status=live }}</ref>

=== Online Model Organism Database ===
[[Xenbase]]<ref name="pmid25313157">{{cite journal | vauthors = Karimi K, Fortriede JD, Lotay VS, Burns KA, Wang DZ, Fisher ME, Pells TJ, James-Zorn C, Wang Y, Ponferrada VG, Chu S, Chaturvedi P, Zorn AM, Vize PD | display-authors = 6 | title = Xenbase: a genomic, epigenomic and transcriptomic model organism database | journal = Nucleic Acids Research | volume = 46 | issue = D1 | pages = D861–D868 | date = January 2018 | pmid = 29059324 | pmc = 5753396 | doi = 10.1093/nar/gkx936 }}</ref> is the [[Generic Model Organism Database|Model Organism Database (MOD)]] for both ''[[Xenopus laevis]]'' and ''[[Xenopus tropicalis]]''.<ref>{{cite web|title=Xenopus model organism database|url=http://www.xenbase.org/|website=Xenbase.org|access-date=2005-01-24|archive-date=2009-09-04|archive-url=https://web.archive.org/web/20090904220935/http://www.xenbase.org/|url-status=live}}</ref>

=== Investigation of human disease genes ===

All modes of ''Xenopus'' research (embryos, cell-free extracts, and oocytes) are commonly used in direct studies of human disease genes and to study the basic science underlying initiation and progression of cancer.<ref>{{cite journal | vauthors = Hardwick LJ, Philpott A | title = An oncologist׳s friend: How Xenopus contributes to cancer research | journal = Developmental Biology | volume = 408 | issue = 2 | pages = 180–187 | date = December 2015 | pmid = 25704511 | pmc = 4684227 | doi = 10.1016/j.ydbio.2015.02.003 | series = Modeling Human Development and Disease in Xenopus }}</ref> ''Xenopus'' embryos for ''in vivo'' studies of human disease gene function:   ''Xenopus'' embryos are large and easily manipulated, and moreover, thousands of embryos can be obtained in a single day.  Indeed, ''Xenopus'' was the first vertebrate animal for which methods were developed to allow rapid analysis of gene function using misexpression (by mRNA injection<ref>{{cite journal | vauthors = Gurdon JB, Lane CD, Woodland HR, Marbaix G | title = Use of frog eggs and oocytes for the study of messenger RNA and its translation in living cells | journal = Nature | volume = 233 | issue = 5316 | pages = 177–182 | date = September 1971 | pmid = 4939175 | doi = 10.1038/233177a0 | s2cid = 4160808 | bibcode = 1971Natur.233..177G }}</ref>).  Injection of mRNA in ''Xenopus'' that led to the cloning of interferon.<ref>{{cite journal | vauthors = Reynolds FH, Premkumar E, Pitha PM | title = Interferon activity produced by translation of human interferon messenger RNA in cell-free ribosomal systems and in Xenopus oöcytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 72 | issue = 12 | pages = 4881–4885 | date = December 1975 | pmid = 1061077 | pmc = 388836 | doi = 10.1073/pnas.72.12.4881 | doi-access = free | bibcode = 1975PNAS...72.4881R }}</ref>  Moreover, the use of morpholino-antisense oligonucleotides for gene knockdowns in vertebrate embryos, which is now widely used, was first developed by Janet Heasman using ''Xenopus''.<ref>{{cite journal | vauthors = Heasman J, Kofron M, Wylie C | title = Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach | journal = Developmental Biology | volume = 222 | issue = 1 | pages = 124–134 | date = June 2000 | pmid = 10885751 | doi = 10.1006/dbio.2000.9720 | doi-access = free }}</ref>

In recent years, these approaches have played in important role in studies of human disease genes.  The mechanism of action for several genes mutated in human cystic kidney disorders (e.g. [[nephronophthisis]]) have been extensively studied in ''Xenopus'' embryos, shedding new light on the link between these disorders, [[ciliogenesis]] and [[Wnt signaling]].<ref>{{cite journal | vauthors = Schäfer T, Pütz M, Lienkamp S, Ganner A, Bergbreiter A, Ramachandran H, Gieloff V, Gerner M, Mattonet C, Czarnecki PG, Sayer JA, Otto EA, Hildebrandt F, Kramer-Zucker A, Walz G | display-authors = 6 | title = Genetic and physical interaction between the NPHP5 and NPHP6 gene products | journal = Human Molecular Genetics | volume = 17 | issue = 23 | pages = 3655–3662 | date = December 2008 | pmid = 18723859 | pmc = 2802281 | doi = 10.1093/hmg/ddn260 }}</ref>  ''Xenopus'' embryos have also provided a rapid test bed for validating newly discovered disease genes.  For example, studies in ''Xenopus'' confirmed and elucidated the role of ''PYCR1'' in [[cutis laxa]] with progeroid features.<ref>{{cite journal | vauthors = Reversade B, Escande-Beillard N, Dimopoulou A, Fischer B, Chng SC, Li Y, Shboul M, Tham PY, Kayserili H, Al-Gazali L, Shahwan M, Brancati F, Lee H, O'Connor BD, Schmidt-von Kegler M, Merriman B, Nelson SF, Masri A, Alkazaleh F, Guerra D, Ferrari P, Nanda A, Rajab A, Markie D, Gray M, Nelson J, Grix A, Sommer A, Savarirayan R, Janecke AR, Steichen E, Sillence D, Hausser I, Budde B, Nürnberg G, Nürnberg P, Seemann P, Kunkel D, Zambruno G, Dallapiccola B, Schuelke M, Robertson S, Hamamy H, Wollnik B, Van Maldergem L, Mundlos S, Kornak U | display-authors = 6 | title = Mutations in PYCR1 cause cutis laxa with progeroid features | journal = Nature Genetics | volume = 41 | issue = 9 | pages = 1016–1021 | date = September 2009 | pmid = 19648921 | doi = 10.1038/ng.413 | s2cid = 10221927 }}</ref>

Transgenic ''Xenopus'' for studying transcriptional regulation of human disease genes:  ''Xenopus'' embryos develop rapidly, so transgenesis in ''Xenopus'' is a rapid and effective method for analyzing genomic regulatory sequences.  In a recent study, mutations in the ''SMAD7'' locus were revealed to associate with human [[colorectal cancer]].  The mutations lay in conserved, but noncoding sequences, suggesting these mutations impacted the patterns of ''SMAD7'' transcription.  To test this hypothesis, the authors used ''Xenopus'' transgenesis, and revealed this genomic region drove expression of [[Green fluorescent protein|GFP]] in the hindgut.  Moreover, transgenics made with the mutant version of this region displayed substantially less expression in the hindgut.<ref>{{cite journal | vauthors = Pittman AM, Naranjo S, Webb E, Broderick P, Lips EH, van Wezel T, Morreau H, Sullivan K, Fielding S, Twiss P, Vijayakrishnan J, Casares F, Qureshi M, Gómez-Skarmeta JL, Houlston RS | display-authors = 6 | title = The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression | journal = Genome Research | volume = 19 | issue = 6 | pages = 987–993 | date = June 2009 | pmid = 19395656 | pmc = 2694486 | doi = 10.1101/gr.092668.109 }}</ref>

''Xenopus'' cell-free extracts for biochemical studies of proteins encoded by human disease genes: A unique advantage of the ''Xenopus'' system is that cytosolic extracts contain both soluble cytoplasmic and nuclear proteins (including chromatin proteins). This is in contrast to cellular extracts prepared from somatic cells with already distinct cellular compartments.  ''Xenopus'' egg extracts have provided numerous insights into the basic biology of cells with particular impact on cell division and the DNA transactions associated with it (see below).

Studies in ''Xenopus'' egg extracts have also yielded critical insights into the mechanism of action of human disease genes associated with genetic instability and elevated cancer risk, such as ataxia telangiectasia, ''[[BRCA1]]'' inherited breast and ovarian cancer, ''Nbs1'' Nijmegen breakage syndrome, ''RecQL4'' Rothmund-Thomson syndrome, ''[[c-Myc]]'' oncogene and FANC proteins ([[Fanconi anemia]]).<ref>{{cite journal | vauthors = Joukov V, Groen AC, Prokhorova T, Gerson R, White E, Rodriguez A, Walter JC, Livingston DM | display-authors = 6 | title = The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly | journal = Cell | volume = 127 | issue = 3 | pages = 539–552 | date = November 2006 | pmid = 17081976 | doi = 10.1016/j.cell.2006.08.053 | s2cid = 17769149 | doi-access = free }}</ref><ref>{{cite journal | vauthors = You Z, Bailis JM, Johnson SA, Dilworth SM, Hunter T | title = Rapid activation of ATM on DNA flanking double-strand breaks | journal = Nature Cell Biology | volume = 9 | issue = 11 | pages = 1311–1318 | date = November 2007 | pmid = 17952060 | doi = 10.1038/ncb1651 | s2cid = 17389213 }}</ref><ref name="Checkpoint signaling from a single">{{cite journal | vauthors = Ben-Yehoyada M, Wang LC, Kozekov ID, Rizzo CJ, Gottesman ME, Gautier J | title = Checkpoint signaling from a single DNA interstrand crosslink | journal = Molecular Cell | volume = 35 | issue = 5 | pages = 704–715 | date = September 2009 | pmid = 19748363 | pmc = 2756577 | doi = 10.1016/j.molcel.2009.08.014 }}</ref><ref>{{cite journal | vauthors = Sobeck A, Stone S, Landais I, de Graaf B, Hoatlin ME | title = The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways | journal = The Journal of Biological Chemistry | volume = 284 | issue = 38 | pages = 25560–25568 | date = September 2009 | pmid = 19633289 | pmc = 2757957 | doi = 10.1074/jbc.M109.007690 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, Galloway DA, Gu W, Gautier J, Dalla-Favera R | display-authors = 6 | title = Non-transcriptional control of DNA replication by c-Myc | journal = Nature | volume = 448 | issue = 7152 | pages = 445–451 | date = July 2007 | pmid = 17597761 | doi = 10.1038/nature05953 | s2cid = 4422771 | bibcode = 2007Natur.448..445D }}</ref>

''Xenopus'' oocytes for studies of gene expression and channel activity related to human disease:  Yet another strength of ''Xenopus'' is the ability to rapidly and easily assay the activity of channel and transporter proteins using expression in oocytes.  This application has also led to important insights into human disease, including studies related to [[Trypanosomatid|trypanosome]] transmission,<ref>{{cite journal | vauthors = Dean S, Marchetti R, Kirk K, Matthews KR | title = A surface transporter family conveys the trypanosome differentiation signal | journal = Nature | volume = 459 | issue = 7244 | pages = 213–217 | date = May 2009 | pmid = 19444208 | pmc = 2685892 | doi = 10.1038/nature07997 | bibcode = 2009Natur.459..213D }}</ref> [[Epilepsy]] with [[ataxia]] and [[sensorineural deafness]]<ref>{{cite journal | vauthors = Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M, Tobin J, Lieberer E, Sterner C, Landoure G, Arora R, Sirimanna T, Thompson D, Cross JH, van't Hoff W, Al Masri O, Tullus K, Yeung S, Anikster Y, Klootwijk E, Hubank M, Dillon MJ, Heitzmann D, Arcos-Burgos M, Knepper MA, Dobbie A, Gahl WA, Warth R, Sheridan E, Kleta R | display-authors = 6 | title = Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations | journal = The New England Journal of Medicine | volume = 360 | issue = 19 | pages = 1960–1970 | date = May 2009 | pmid = 19420365 | pmc = 3398803 | doi = 10.1056/NEJMoa0810276 }}</ref>  Catastrophic [[cardiac arrhythmia]] ([[Long-QT syndrome]])<ref>{{cite journal | vauthors = Gustina AS, Trudeau MC | title = A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channels | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 31 | pages = 13082–13087 | date = August 2009 | pmid = 19651618 | pmc = 2722319 | doi = 10.1073/pnas.0900180106 | doi-access = free | bibcode = 2009PNAS..10613082G }}</ref>  and Megalencephalic leukoencephalopathy.<ref>{{cite journal | vauthors = Duarri A, Teijido O, López-Hernández T, Scheper GC, Barriere H, Boor I, Aguado F, Zorzano A, Palacín M, Martínez A, Lukacs GL, van der Knaap MS, Nunes V, Estévez R | display-authors = 6 | title = Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects | journal = Human Molecular Genetics | volume = 17 | issue = 23 | pages = 3728–3739 | date = December 2008 | pmid = 18757878 | pmc = 2581428 | doi = 10.1093/hmg/ddn269 }}</ref>

Gene editing by the CRISPR/CAS system has recently been demonstrated in ''Xenopus'' ''tropicalis''<ref>{{cite journal | vauthors = Blitz IL, Biesinger J, Xie X, Cho KW | title = Biallelic genome modification in F(0) Xenopus tropicalis embryos using the CRISPR/Cas system | journal = Genesis | volume = 51 | issue = 12 | pages = 827–834 | date = December 2013 | pmid = 24123579 | pmc = 4039559 | doi = 10.1002/dvg.22719 }}</ref><ref>{{cite journal | vauthors = Nakayama T, Fish MB, Fisher M, Oomen-Hajagos J, Thomsen GH, Grainger RM | title = Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis | journal = Genesis | volume = 51 | issue = 12 | pages = 835–843 | date = December 2013 | pmid = 24123613 | pmc = 3947545 | doi = 10.1002/dvg.22720 }}</ref> and ''Xenopus laevis''.<ref>{{cite journal | vauthors = Wang F, Shi Z, Cui Y, Guo X, Shi YB, Chen Y | title = Targeted gene disruption in Xenopus laevis using CRISPR/Cas9 | language = En | journal = Cell & Bioscience | volume = 5 | issue = 1 | page = 15 | date = 2015-04-14 | pmid = 25897376 | pmc = 4403895 | doi = 10.1186/s13578-015-0006-1 | doi-access = free }}</ref> This technique is being used to screen the effects of human disease genes in ''Xenopus'' and the system is sufficiently efficient to study the effects within the same embryos that have been manipulated.<ref>{{cite journal | vauthors = Bhattacharya D, Marfo CA, Li D, Lane M, Khokha MK | title = CRISPR/Cas9: An inexpensive, efficient loss of function tool to screen human disease genes in Xenopus | journal = Developmental Biology | volume = 408 | issue = 2 | pages = 196–204 | date = December 2015 | pmid = 26546975 | pmc = 4684459 | doi = 10.1016/j.ydbio.2015.11.003 | series = Modeling Human Development and Disease in Xenopus }}</ref>

=== Investigation of fundamental biological processes ===

[[Signal transduction]]:  ''Xenopus'' embryos and cell-free extracts are widely used for basic research in signal transduction.  In just the last few years, ''Xenopus'' embryos have provided crucial insights into the mechanisms of TGF-beta and Wnt signal transduction.  For example, ''Xenopus'' embryos were used to identify the enzymes that control ubiquitination of Smad4,<ref>{{cite journal | vauthors = Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, Inui M, Moro S, Modena N, Argenton F, Newfeld SJ, Piccolo S | display-authors = 6 | title = FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination | journal = Cell | volume = 136 | issue = 1 | pages = 123–135 | date = January 2009 | pmid = 19135894 | doi = 10.1016/j.cell.2008.10.051 | s2cid = 16458957 | doi-access = free }}</ref> and to demonstrate direct links between TGF-beta superfamily signaling pathways and other important networks, such as the MAP kinase pathway<ref>{{cite journal | vauthors = Cordenonsi M, Montagner M, Adorno M, Zacchigna L, Martello G, Mamidi A, Soligo S, Dupont S, Piccolo S | display-authors = 6 | title = Integration of TGF-beta and Ras/MAPK signaling through p53 phosphorylation | journal = Science | volume = 315 | issue = 5813 | pages = 840–843 | date = February 2007 | pmid = 17234915 | doi = 10.1126/science.1135961 | s2cid = 83962686 | bibcode = 2007Sci...315..840C | doi-access = free }}</ref> and the Wnt pathway.<ref>{{cite journal | vauthors = Fuentealba LC, Eivers E, Ikeda A, Hurtado C, Kuroda H, Pera EM, De Robertis EM | title = Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal | journal = Cell | volume = 131 | issue = 5 | pages = 980–993 | date = November 2007 | pmid = 18045539 | pmc = 2200633 | doi = 10.1016/j.cell.2007.09.027 }}</ref>  Moreover, new methods using egg extracts revealed novel, important targets of the Wnt/GSK3 destruction complex.<ref>{{cite journal | vauthors = Kim NG, Xu C, Gumbiner BM | title = Identification of targets of the Wnt pathway destruction complex in addition to beta-catenin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 13 | pages = 5165–5170 | date = March 2009 | pmid = 19289839 | pmc = 2663984 | doi = 10.1073/pnas.0810185106 | doi-access = free | bibcode = 2009PNAS..106.5165K }}</ref>

[[Cell division]]:  ''Xenopus'' egg extracts have allowed the study of many complicated cellular events ''in vitro''.  Because egg cytosol can support successive cycling between mitosis and interphase ''in vitro'', it has been critical to diverse studies of cell division.  For example, the small GTPase Ran was first found to regulate interphase nuclear transport, but ''Xenopus'' egg extracts revealed the critical role of Ran GTPase in mitosis independent of its role in interphase nuclear transport.<ref>{{cite journal | vauthors = Kaláb P, Pralle A, Isacoff EY, Heald R, Weis K | title = Analysis of a RanGTP-regulated gradient in mitotic somatic cells | journal = Nature | volume = 440 | issue = 7084 | pages = 697–701 | date = March 2006 | pmid = 16572176 | doi = 10.1038/nature04589 | s2cid = 4398374 | bibcode = 2006Natur.440..697K }}</ref> Similarly, the cell-free extracts were used to model nuclear envelope assembly from chromatin, revealing the function of RanGTPase in regulating nuclear envelope reassembly after mitosis.<ref>{{cite journal | vauthors = Tsai MY, Wang S, Heidinger JM, Shumaker DK, Adam SA, Goldman RD, Zheng Y | title = A mitotic lamin B matrix induced by RanGTP required for spindle assembly | journal = Science | volume = 311 | issue = 5769 | pages = 1887–1893 | date = March 2006 | pmid = 16543417 | doi = 10.1126/science.1122771 | s2cid = 12219529 | bibcode = 2006Sci...311.1887T }}</ref>  More recently, using ''Xenopus'' egg extracts, it was possible to demonstrate the mitosis-specific function of the nuclear lamin B in regulating spindle morphogenesis<ref>{{cite journal | vauthors = Ma L, Tsai MY, Wang S, Lu B, Chen R, Yates JR, Zhu X, Zheng Y | display-authors = 6 | title = Requirement for Nudel and dynein for assembly of the lamin B spindle matrix | journal = Nature Cell Biology | volume = 11 | issue = 3 | pages = 247–256 | date = March 2009 | pmid = 19198602 | pmc = 2699591 | doi = 10.1038/ncb1832 }}</ref> and to identify new proteins that mediate kinetochore attachment to microtubules.<ref>{{cite journal | vauthors = Emanuele MJ, Stukenberg PT | title = Xenopus Cep57 is a novel kinetochore component involved in microtubule attachment | journal = Cell | volume = 130 | issue = 5 | pages = 893–905 | date = September 2007 | pmid = 17803911 | doi = 10.1016/j.cell.2007.07.023 | s2cid = 17520550 | doi-access = free }}</ref> [[Cell-free system]]s have recently become practical investigatory tools, and ''Xenopus'' oocytes are often the source of the extracts used. This has produced significant results in understanding [[mitotic]] oscillation and [[microtubule]]s.<ref name="Noireaux-Liu-2020">{{cite journal | vauthors = Noireaux V, Liu AP | title = The New Age of Cell-Free Biology | journal = Annual Review of Biomedical Engineering | volume = 22 | issue = 1 | pages = 51–77 | date = June 2020 | pmid = 32151150 | doi = 10.1146/annurev-bioeng-092019-111110 | publisher = [[Annual Reviews (publisher)|Annual Reviews]] | s2cid = 212652742 | doi-access = free }}</ref>

[[Embryonic development]]:  ''Xenopus'' embryos are widely used in developmental biology. A summary of recent advances made by ''Xenopus'' research in recent years would include:

#[[Epigenetics]] of cell fate specification<ref>{{cite journal | vauthors = Akkers RC, van Heeringen SJ, Jacobi UG, Janssen-Megens EM, Françoijs KJ, Stunnenberg HG, Veenstra GJ | title = A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos | journal = Developmental Cell | volume = 17 | issue = 3 | pages = 425–434 | date = September 2009 | pmid = 19758566 | pmc = 2746918 | doi = 10.1016/j.devcel.2009.08.005 }}</ref> and epigenome reference maps<ref>{{cite journal | vauthors = Hontelez S, van Kruijsbergen I, Georgiou G, van Heeringen SJ, Bogdanovic O, Lister R, Veenstra GJ | title = Embryonic transcription is controlled by maternally defined chromatin state | journal = Nature Communications | volume = 6 | article-number = 10148 | date = December 2015 | pmid = 26679111 | pmc = 4703837 | doi = 10.1038/ncomms10148 | bibcode = 2015NatCo...610148H }}</ref>
#[[microRNA]] in germ layer patterning and eye development<ref>{{cite journal | vauthors = Walker JC, Harland RM | title = microRNA-24a is required to repress apoptosis in the developing neural retina | journal = Genes & Development | volume = 23 | issue = 9 | pages = 1046–1051 | date = May 2009 | pmid = 19372388 | pmc = 2682950 | doi = 10.1101/gad.1777709 }}</ref><ref>{{cite journal | vauthors = Rosa A, Spagnoli FM, Brivanlou AH | title = The miR-430/427/302 family controls mesendodermal fate specification via species-specific target selection | journal = Developmental Cell | volume = 16 | issue = 4 | pages = 517–527 | date = April 2009 | pmid = 19386261 | doi = 10.1016/j.devcel.2009.02.007 | doi-access = free }}</ref>
#Link between [[Wnt signaling]] and [[telomerase]]<ref>{{cite journal | vauthors = Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M, Chang W, Meng Z, Cheung P, Ji H, McLaughlin M, Veenstra TD, Nusse R, McCrea PD, Artandi SE | display-authors = 6 | title = Telomerase modulates Wnt signalling by association with target gene chromatin | journal = Nature | volume = 460 | issue = 7251 | pages = 66–72 | date = July 2009 | pmid = 19571879 | pmc = 4349391 | doi = 10.1038/nature08137 | bibcode = 2009Natur.460...66P }}</ref>
#Development of the [[vasculature]]<ref>{{cite journal | vauthors = De Val S, Chi NC, Meadows SM, Minovitsky S, Anderson JP, Harris IS, Ehlers ML, Agarwal P, Visel A, Xu SM, Pennacchio LA, Dubchak I, Krieg PA, Stainier DY, Black BL | display-authors = 6 | title = Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors | journal = Cell | volume = 135 | issue = 6 | pages = 1053–1064 | date = December 2008 | pmid = 19070576 | pmc = 2782666 | doi = 10.1016/j.cell.2008.10.049 }}</ref>
#Gut morphogenesis<ref>{{cite journal | vauthors = Li Y, Rankin SA, Sinner D, Kenny AP, Krieg PA, Zorn AM | title = Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling | journal = Genes & Development | volume = 22 | issue = 21 | pages = 3050–3063 | date = November 2008 | pmid = 18981481 | pmc = 2577796 | doi = 10.1101/gad.1687308 }}</ref>
#Contact inhibition and [[neural crest]] cell migration<ref>{{cite journal | vauthors = Carmona-Fontaine C, Matthews HK, Kuriyama S, Moreno M, Dunn GA, Parsons M, Stern CD, Mayor R | display-authors = 6 | title = Contact inhibition of locomotion in vivo controls neural crest directional migration | journal = Nature | volume = 456 | issue = 7224 | pages = 957–961 | date = December 2008 | pmid = 19078960 | pmc = 2635562 | doi = 10.1038/nature07441 | bibcode = 2008Natur.456..957C }}</ref> and the generation of neural crest from pluripotent blastula cells<ref>{{cite journal | vauthors = Buitrago-Delgado E, Nordin K, Rao A, Geary L, LaBonne C | title = NEURODEVELOPMENT. Shared regulatory programs suggest retention of blastula-stage potential in neural crest cells | journal = Science | volume = 348 | issue = 6241 | pages = 1332–1335 | date = June 2015 | pmid = 25931449 | pmc = 4652794 | doi = 10.1126/science.aaa3655 }}</ref>
#{{visible anchor|Developmental fate}} - Role of ''[[Notch signaling pathway|Notch]]'': Dorsky et al 1995 elucidated a pattern of expression followed by downregulation<ref name="Gaiano-Fishell-2002">{{cite journal | vauthors = Gaiano N, Fishell G | title = The role of notch in promoting glial and neural stem cell fates | journal = Annual Review of Neuroscience | volume = 25 | issue = 1 | pages = 471–490 | year = 2002 | pmid = 12052917 | doi = 10.1146/annurev.neuro.25.030702.130823 | publisher = [[Annual Reviews (publisher)|Annual Reviews]] | s2cid = 15691580 }}</ref>

[[DNA replication]]:  ''Xenopus'' cell-free extracts also support the synchronous assembly and the activation of origins of DNA replication. They have been instrumental in characterizing the biochemical function of the prereplicative complex, including MCM proteins.<ref>{{cite journal | vauthors = Tsuji T, Lau E, Chiang GG, Jiang W | title = The role of Dbf4/Drf1-dependent kinase Cdc7 in DNA-damage checkpoint control | journal = Molecular Cell | volume = 32 | issue = 6 | pages = 862–869 | date = December 2008 | pmid = 19111665 | pmc = 4556649 | doi = 10.1016/j.molcel.2008.12.005 }}</ref><ref>{{cite journal | vauthors = Xu X, Rochette PJ, Feyissa EA, Su TV, Liu Y | title = MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication | journal = The EMBO Journal | volume = 28 | issue = 19 | pages = 3005–3014 | date = October 2009 | pmid = 19696745 | pmc = 2760112 | doi = 10.1038/emboj.2009.235 }}</ref>

[[DNA damage]] response: Cell-free extracts have been instrumental to unravel the signaling pathways activated in response to DNA double-strand breaks (ATM), replication fork stalling (ATR) or DNA interstrand crosslinks (FA proteins and ATR). Notably, several mechanisms and components of these signal transduction pathways were first identified in ''Xenopus''.<ref name="Checkpoint signaling from a single"/><ref>{{cite journal | vauthors = Räschle M, Knipscheer P, Knipsheer P, Enoiu M, Angelov T, Sun J, Griffith JD, Ellenberger TE, Schärer OD, Walter JC | display-authors = 6 | title = Mechanism of replication-coupled DNA interstrand crosslink repair | journal = Cell | volume = 134 | issue = 6 | pages = 969–980 | date = September 2008 | pmid = 18805090 | pmc = 2748255 | doi = 10.1016/j.cell.2008.08.030 | author-link9 = Orlando D. Schärer }}</ref><ref>{{cite journal | vauthors = MacDougall CA, Byun TS, Van C, Yee MC, Cimprich KA | title = The structural determinants of checkpoint activation | journal = Genes & Development | volume = 21 | issue = 8 | pages = 898–903 | date = April 2007 | pmid = 17437996 | pmc = 1847708 | doi = 10.1101/gad.1522607 }}</ref>

[[Apoptosis]]:  ''Xenopus'' oocytes provide a tractable model for biochemical studies of apoptosis.  Recently, oocytes were used recently to study the biochemical mechanisms of caspase-2 activation;  importantly, this mechanism turns out to be conserved in mammals.<ref>{{cite journal | vauthors = Nutt LK, Buchakjian MR, Gan E, Darbandi R, Yoon SY, Wu JQ, Miyamoto YJ, Gibbons JA, Gibbon JA, Andersen JL, Freel CD, Tang W, He C, Kurokawa M, Wang Y, Margolis SS, Fissore RA, Kornbluth S | display-authors = 6 | title = Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2 | journal = Developmental Cell | volume = 16 | issue = 6 | pages = 856–866 | date = June 2009 | pmid = 19531356 | pmc = 2698816 | doi = 10.1016/j.devcel.2009.04.005 }}</ref>

[[Regenerative medicine]]:  In recent years, tremendous interest in developmental biology has been stoked by the promise of regenerative medicine.  ''Xenopus'' has played a role here, as well.  For example,  expression of seven transcription factors in pluripotent ''Xenopus'' cells rendered those cells able to develop into functional eyes when implanted into ''Xenopus'' embryos, providing potential insights into the repair of retinal degeneration or damage.<ref>{{cite journal | vauthors = Viczian AS, Solessio EC, Lyou Y, Zuber ME | title = Generation of functional eyes from pluripotent cells | journal = PLOS Biology | volume = 7 | issue = 8 | article-number = e1000174 | date = August 2009 | pmid = 19688031 | pmc = 2716519 | doi = 10.1371/journal.pbio.1000174 | doi-access = free }}</ref>  In a vastly different study, ''Xenopus'' embryos was used to study the effects of tissue tension on morphogenesis,<ref>{{cite journal | vauthors = Dzamba BJ, Jakab KR, Marsden M, Schwartz MA, DeSimone DW | title = Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization | journal = Developmental Cell | volume = 16 | issue = 3 | pages = 421–432 | date = March 2009 | pmid = 19289087 | pmc = 2682918 | doi = 10.1016/j.devcel.2009.01.008 }}</ref> an issue that will be critical for ''in vitro'' tissue engineering. ''Xenopus'' species are important model organisms for the study of spinal cord regeneration, because while capable of regeneration in their larval stages, ''Xenopus'' lose this capacity in early metamorphosis.<ref>{{cite journal | vauthors = Beattie MS, Bresnahan JC, Lopate G | title = Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs | journal = Journal of Neurobiology | volume = 21 | issue = 7 | pages = 1108–1122 | date = October 1990 | pmid = 2258724 | doi = 10.1002/neu.480210714 }}</ref>

[[Physiology]]:  The directional beating of multiciliated cells is essential to development and homeostasis in the central nervous system, the airway, and the oviduct.  The multiciliated cells of the ''Xenopus'' epidermis have recently been developed as the first ''in vivo'' test-bed for live-cell studies of such ciliated tissues, and these studies have provided important insights into the biomechanical and molecular control of directional beating.<ref>{{cite journal | vauthors = Park TJ, Mitchell BJ, Abitua PB, Kintner C, Wallingford JB | title = Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells | journal = Nature Genetics | volume = 40 | issue = 7 | pages = 871–879 | date = July 2008 | pmid = 18552847 | pmc = 2771675 | doi = 10.1038/ng.104 }}</ref><ref>{{cite journal | vauthors = Mitchell B, Jacobs R, Li J, Chien S, Kintner C | title = A positive feedback mechanism governs the polarity and motion of motile cilia | journal = Nature | volume = 447 | issue = 7140 | pages = 97–101 | date = May 2007 | pmid = 17450123 | doi = 10.1038/nature05771 | s2cid = 4415593 | bibcode = 2007Natur.447...97M }}</ref>

[[Actin]]: Another result from cell-free ''Xenopus'' oocyte extracts has been improved understanding of actin.<ref name="Noireaux-Liu-2020" />

=== Small molecule screens to develop novel therapies ===

Because huge amounts of material are easily obtained, all modalities of ''Xenopus'' research are now being used for small-molecule based screens.

[[Chemical genetics]] of vascular growth in ''Xenopus'' tadpoles:  Given the important role of neovascularization in cancer progression, ''Xenopus'' embryos were recently used to identify new small molecules inhibitors of blood vessel growth.  Notably, compounds identified in ''Xenopus'' were effective in mice.<ref>{{cite journal | vauthors = Kälin RE, Bänziger-Tobler NE, Detmar M, Brändli AW | title = An in vivo chemical library screen in Xenopus tadpoles reveals novel pathways involved in angiogenesis and lymphangiogenesis | journal = Blood | volume = 114 | issue = 5 | pages = 1110–1122 | date = July 2009 | pmid = 19478043 | pmc = 2721788 | doi = 10.1182/blood-2009-03-211771 }}</ref><ref>{{cite journal | vauthors = Ny A, Koch M, Vandevelde W, Schneider M, Fischer C, Diez-Juan A, Neven E, Geudens I, Maity S, Moons L, Plaisance S, Lambrechts D, Carmeliet P, Dewerchin M | display-authors = 6 | title = Role of VEGF-D and VEGFR-3 in developmental lymphangiogenesis, a chemicogenetic study in Xenopus tadpoles | journal = Blood | volume = 112 | issue = 5 | pages = 1740–1749 | date = September 2008 | pmid = 18474726 | doi = 10.1182/blood-2007-08-106302 | s2cid = 14663578 | doi-access = free }}</ref>  Notably, frog embryos figured prominently in a study that used evolutionary principles to identify a novel vascular disrupting agent that may have chemotherapeutic potential.<ref>{{cite journal | vauthors = Cha HJ, Byrom M, Mead PE, Ellington AD, Wallingford JB, Marcotte EM | title = Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent | journal = PLOS Biology | volume = 10 | issue = 8 | article-number = e1001379 | date = 2012-01-01 | pmid = 22927795 | pmc = 3423972 | doi = 10.1371/journal.pbio.1001379 | doi-access = free }}</ref>  That work was featured in the New York Times Science Times<ref name="NYT">{{cite news|title=Gene Tests in Yeast Aid Work on Cancer|url=https://www.nytimes.com/2012/08/21/health/research/clues-to-fighting-cancer-are-found-in-the-genes-of-yeast.html|newspaper=The New York Times|date=2012-08-21|vauthors=Zimmer C|archive-date=2017-06-08|access-date=2017-02-28|archive-url=https://web.archive.org/web/20170608201523/http://www.nytimes.com/2012/08/21/health/research/clues-to-fighting-cancer-are-found-in-the-genes-of-yeast.html|url-status=live}}</ref>

''In vivo'' testing of potential [[endocrine disruptors]] in transgenic ''Xenopus'' embryos; A high-throughput assay for thyroid disruption has recently been developed using transgenic ''Xenopus'' embryos.<ref name="renamed_from_29_on_20121012150200">{{cite journal | vauthors = Fini JB, Le Mevel S, Turque N, Palmier K, Zalko D, Cravedi JP, Demeneix BA | title = An in vivo multiwell-based fluorescent screen for monitoring vertebrate thyroid hormone disruption | journal = Environmental Science & Technology | volume = 41 | issue = 16 | pages = 5908–5914 | date = August 2007 | pmid = 17874805 | doi = 10.1021/es0704129 | bibcode = 2007EnST...41.5908F }}</ref>

Small molecule screens in ''Xenopus'' egg extracts:  Egg extracts provide ready analysis of molecular biological processes and can rapidly screened.  This approach was used to identify novel inhibitors of proteasome-mediated protein degradation and DNA repair enzymes.<ref name="pmid18176557">{{cite journal | vauthors = Dupré A, Boyer-Chatenet L, Sattler RM, Modi AP, Lee JH, Nicolette ML, Kopelovich L, Jasin M, Baer R, Paull TT, Gautier J | title = A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex | journal = Nature Chemical Biology | volume = 4 | issue = 2 | pages = 119–25 | date = February 2008 | pmid = 18176557 | pmc = 3065498 | doi = 10.1038/nchembio.63 }}</ref><ref name="pmid19048618">{{cite journal | vauthors = Landais I, Sobeck A, Stone S, LaChapelle A, Hoatlin ME | title = A novel cell-free screen identifies a potent inhibitor of the Fanconi anemia pathway | journal = International Journal of Cancer | volume = 124 | issue = 4 | pages = 783–92 | date = February 2009 | pmid = 19048618 | doi = 10.1002/ijc.24039 | s2cid = 33589304 | doi-access = free }}</ref>

=== Genetic studies ===

While ''Xenopus laevis'' is the most commonly used species for [[developmental biology]] studies, genetic studies, especially forward genetic studies, can be complicated by their [[ploidy|pseudotetraploid]] [[genome]].  ''[[Xenopus tropicalis]]'' provides a simpler model for genetic studies, having a [[ploidy|diploid]] genome.

=== Gene expression knockdown techniques ===
The expression of genes can be reduced by a variety of means, for example by using antisense oligonucleotides targeting specific mRNA molecules. DNA oligonucleotides complementary to specific mRNA molecules are often chemically modified to improve their stability ''in vivo''. The chemical modifications used for this purpose include phosphorothioate, 2'-O-methyl, morpholino, MEA phosphoramidate and DEED phosphoramidate.<ref name=":0">{{cite journal | vauthors = Dagle JM, Weeks DL | title = Oligonucleotide-based strategies to reduce gene expression | journal = Differentiation; Research in Biological Diversity | volume = 69 | issue = 2–3 | pages = 75–82 | date = December 2001 | pmid = 11798068 | doi = 10.1046/j.1432-0436.2001.690201.x }}</ref>

==== Morpholino oligonucleotides ====
{{Main|Morpholino}}

Morpholino oligos are used in both ''X. laevis'' and ''X. tropicalis'' to probe the function of a protein by observing the results of eliminating the protein's activity.<ref name=":0" /><ref name=":1">{{cite journal | vauthors = Blum M, De Robertis EM, Wallingford JB, Niehrs C | title = Morpholinos: Antisense and Sensibility | journal = Developmental Cell | volume = 35 | issue = 2 | pages = 145–149 | date = October 2015 | pmid = 26506304 | doi = 10.1016/j.devcel.2015.09.017 | doi-access = free }}</ref> For example, a set of ''X. tropicalis'' genes has been screened in this fashion.<ref>{{cite journal | vauthors = Rana AA, Collart C, Gilchrist MJ, Smith JC | title = Defining synphenotype groups in Xenopus tropicalis by use of antisense morpholino oligonucleotides | journal = PLOS Genetics | volume = 2 | issue = 11 | article-number = e193 | date = November 2006 | pmid = 17112317 | pmc = 1636699 | doi = 10.1371/journal.pgen.0020193 | doi-access = free }}<br />{{cite web |url=http://www.gurdon.cam.ac.uk/~smithlab/screens/Xenopus-morpholino-pilot/ |title=A ''Xenopus tropicalis'' antisense morpholino screen |date=4 March 2014 |publisher=Gurdon Institute |access-date=17 January 2007 |archive-date=12 June 2018 |archive-url=https://web.archive.org/web/20180612164223/https://www.gurdon.cam.ac.uk/~smithlab/screens/Xenopus-morpholino-pilot/ }}</ref>

Morpholino oligos (MOs) are short, antisense oligos made of modified nucleotides. MOs can knock down gene expression by inhibiting mRNA translation, blocking RNA splicing, or inhibiting miRNA activity and maturation. MOs have proven to be effective knockdown tools in developmental biology experiments and RNA-blocking reagents for cells in culture. MOs do not degrade their RNA targets, but instead act via a steric blocking mechanism RNAseH-independent manner. They remain stable in cells and do not induce immune responses. Microinjection of MOs in early ''Xenopus'' embryos can suppress gene expression in a targeted manner.

Like all antisense approaches, different MOs can have different efficacy, and may cause off-target, non-specific effects. Often, several MOs need to be tested to find an effective target sequence. Rigorous controls are used to demonstrate specificity,<ref name=":1" /> including:
* Phenocopy of genetic mutation
* Verification of reduced protein by western or immunostaining
* mRNA rescue by adding back a mRNA immune to the MO
* use of 2 different MOs (translation blocking and splice blocking) 
* injection of control MOs
[[Xenbase]] provides a searchable catalog of over 2000 MOs that have been specifically used in Xenopus'' research.'' The data is searchable via sequence, gene symbol and various synonyms (as used in different publications).<ref>[http://www.xenbase.org/reagents/morpholino.do Xenbase] {{Webarchive|url=https://web.archive.org/web/20180612140114/http://www.xenbase.org/reagents/morpholino.do |date=2018-06-12 }}</ref> Xenbase maps the MOs to the latest ''Xenopus'' genomes in GBrowse, predicts 'off-target' hits, and lists all ''Xenopus'' literature in which the morpholino has been published.

== References ==
{{Reflist|30em}}

== External links ==
*[http://www.xenbase.org/ Xenbase] {{Webarchive|url=https://web.archive.org/web/20090904220935/http://www.xenbase.org/ |date=2009-09-04 }} ~ A ''Xenopus laevis'' and ''tropicalis'' Web Resource

{{Model Organisms}}
{{Taxonbar|from=Q1342298}}
{{Authority control}}

[[Category:Pipidae]]
[[Category:Xenopus| ]]
[[Category:Amphibian genera]]
[[Category:Amphibians of Sub-Saharan Africa]]
[[Category:Vertebrate developmental biology]]
[[Category:Animal models]]
[[Category:Taxa named by Johann Andreas Wagner]]
[[Category:Extant Oligocene first appearances]]