Xenopus
Temporal range:
Xenopus laevis
Scientific classification Edit this classification
Domain: Eukaryota
Kingdom: Animalia
Phylum: Chordata
Class: Amphibia
Order: Anura
Family: Pipidae
Genus: Xenopus
Wagler 1827
Species

See text

Xenopus (/ˈzɛnəpəs/[1][2]) (Gk., ξενος, xenos = strange, πους, pous = 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 organisms for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects.[3][4][5]

The genus is also known for its polyploidy, with some species having up to 12 sets of chromosomes.

Characteristics

Xenopus laevis is a rather inactive creature. It is incredibly hardy 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).[6] 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 claws.

The frog's eyes are on top of the head, looking upwards. The pupils are circular. They have no moveable eyelids, tongues (rather it is completely attached to the floor of the mouth[6]) or eardrums (similarly to Pipa pipa, the common Suriname toad[7]).[8]

Unlike most amphibians, they have no haptoglobin in their blood.[8]

Behaviour

Xenopus species are entirely 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 lakes, rivers, swamps, potholes in streams, and man-made reservoirs.[8]

Adult frogs are usually both predators 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 sacs, they make clicks (brief pulses of sound) underwater (again similar to Pipa pipa).[7] Males establish a hierarchy of social dominance in which primarily one male has the right to make the advertisement call.[9] 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.[10] The Xenopus species are also active during the twilight (or crepuscular) hours.[8]

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.[8]

Species

A Xenopus laevis female with a batch of freshly laid eggs and a Xenopus tropicalis male

Extant species

Fossil species

The following fossil species have been described:[11]

Model organism for biological research

Like many other frogs, they are often used in laboratory as research subjects.[6] Xenopus embryos and eggs are a popular model system for a wide variety of biological studies.[4][5] 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.[4][5]

Xenopus has long been an important tool for in vivo studies in molecular, cell, and developmental biology of vertebrate animals.[5] However, the wide breadth of Xenopus research stems from the additional fact that 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.[4] Xenopus is also a unique system for analyses of genome evolution and whole genome duplication in vertebrates,[12] as different Xenopus species form a ploidy series formed by interspecific hybridization.[13]

In 1931, Lancelot Hogben noted that Xenopus laevis females ovulated when injected with the urine of pregnant women.[14] This led to a pregnancy test that was later refined by South African researchers Hillel Abbe Shapiro and Harry Zwarenstein.[15] 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.[16] From the 1930s to the 1950s, thousands of frogs were exported across the world for use in these pregnancy tests.[17]

The National Xenopus Resource of the Marine Biological Laboratory is an in vivo repository for transgenic and mutant strains and a training center.[18]

Online Model Organism Database

Xenbase[19] is the Model Organism Database (MOD) for both Xenopus laevis and Xenopus tropicalis.[20]

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.[21] 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[22]). Injection of mRNA in Xenopus that led to the cloning of interferon.[23] 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.[24]

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.[25] 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.[26]

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 GFP in the hindgut. Moreover, transgenics made with the mutant version of this region displayed substantially less expression in the hindgut.[27]

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).[28][29][30][31][32]

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 trypanosome transmission,[33] Epilepsy with ataxia and sensorineural deafness[34] Catastrophic cardiac arrhythmia (Long-QT syndrome)[35] and Megalencephalic leukoencephalopathy.[36]

Gene editing by the CRISPR/CAS system has recently been demonstrated in Xenopus tropicalis[37][38] and Xenopus laevis.[39] 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.[40]

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,[41] and to demonstrate direct links between TGF-beta superfamily signaling pathways and other important networks, such as the MAP kinase pathway[42] and the Wnt pathway.[43] Moreover, new methods using egg extracts revealed novel, important targets of the Wnt/GSK3 destruction complex.[44]

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.[45] 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.[46] More recently, using Xenopus egg extracts, it was possible to demonstrate the mitosis-specific function of the nuclear lamin B in regulating spindle morphogenesis[47] and to identify new proteins that mediate kinetochore attachment to microtubules.[48] Cell-free systems 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 microtubules.[49]

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

  1. Epigenetics of cell fate specification[50] and epigenome reference maps[51]
  2. microRNA in germ layer patterning and eye development[52][53]
  3. Link between Wnt signaling and telomerase[54]
  4. Development of the vasculature[55]
  5. Gut morphogenesis[56]
  6. Contact inhibition and neural crest cell migration[57] and the generation of neural crest from pluripotent blastula cells[58]
  7. Developmental fate - Role of Notch: Dorsky et al 1995 elucidated a pattern of expression followed by downregulation[59]

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.[60][61]

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.[30][62][63]

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.[64]

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.[65] In a vastly different study, Xenopus embryos was used to study the effects of tissue tension on morphogenesis,[66] 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.[67]

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.[68][69]

Actin: Another result from cell-free Xenopus oocyte extracts has been improved understanding of actin.[49]

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.[70][71] Notably, frog embryos figured prominently in a study that used evolutionary principles to identify a novel vascular disrupting agent that may have chemotherapeutic potential.[72] That work was featured in the New York Times Science Times[73]

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.[74]

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.[75][76]

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 pseudotetraploid genome. Xenopus tropicalis provides a simpler model for genetic studies, having a 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.[77]

Morpholino oligonucleotides

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.[77][78] For example, a set of X. tropicalis genes has been screened in this fashion.[79]

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,[78] 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).[80] 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

  1. ↑ "Xenopus". Lexico UK English Dictionary. Oxford University Press. Archived from the original on 2020-03-22.
  2. ↑ "Xenopus". Merriam-Webster.com Dictionary. Retrieved 2016-01-21.
  3. ↑ Nenni MJ, Fisher ME, James-Zorn C, Pells TJ, Ponferrada V, Chu S, et al. (2019). "Xenbase: Facilitating the Use of Xenopus to Model Human Disease". Frontiers in Physiology. 10: 154. doi:10.3389/fphys.2019.00154. PMC 6399412. PMID 30863320.
  4. 1 2 3 4 Wallingford JB, Liu KJ, Zheng Y (March 2010). "Xenopus". Current Biology. 20 (6): R263–R264. doi:10.1016/j.cub.2010.01.012. PMID 20334828.
  5. 1 2 3 4 Harland RM, Grainger RM (December 2011). "Xenopus research: metamorphosed by genetics and genomics". Trends in Genetics. 27 (12): 507–515. doi:10.1016/j.tig.2011.08.003. PMC 3601910. PMID 21963197.
  6. 1 2 3 "IACUC Learning Module — Xenopus laevis". University of Arizona. Archived from the original on 2010-06-26. Retrieved 2009-10-11.
  7. 1 2 Roots C (2006). Nocturnal animals. Greenwood Press. p. 19. ISBN 978-0-313-33546-4.
  8. 1 2 3 4 5 Passmore NI, Carruthers VC (1979). South African Frogs. Johannesburg: Witwatersrand University Press. pp. 42–43. ISBN 0-85494-525-3.
  9. ↑ Tobias ML, Corke A, Korsh J, Yin D, Kelley DB (November 2010). "Vocal competition in male Xenopus laevis frogs". Behavioral Ecology and Sociobiology. 64 (11): 1791–1803. doi:10.1007/s00265-010-0991-3. PMC 3064475. PMID 21442049.
  10. ↑ Tobias ML, Viswanathan SS, Kelley DB (February 1998). "Rapping, a female receptive call, initiates male-female duets in the South African clawed frog". Proceedings of the National Academy of Sciences of the United States of America. 95 (4): 1870–1875. Bibcode:1998PNAS...95.1870T. doi:10.1073/pnas.95.4.1870. PMC 19205. PMID 9465109.
  11. ↑ [ Xenopus] at Fossilworks.org
  12. ↑ Session AM, Uno Y, Kwon T, Chapman JA, Toyoda A, Takahashi S, et al. (October 2016). "Genome evolution in the allotetraploid frog Xenopus laevis". Nature. 538 (7625): 336–343. Bibcode:2016Natur.538..336S. doi:10.1038/nature19840. PMC 5313049. PMID 27762356.
  13. ↑ Schmid M, Evans BJ, Bogart JP (2015). "Polyploidy in Amphibia". Cytogenetic and Genome Research. 145 (3–4): 315–330. doi:10.1159/000431388. PMID 26112701.
  14. ↑ Hogben L, Charles E, Slome D (1931). "Studies on the pituitary. 8. The relation of the pituitary gland to calcium metabolism and ovarian function in Xenopus". Journal of Experimental Biology. 8: 345–54. doi:10.1242/jeb.8.4.345.
  15. ↑ Elkan ER (December 1938). "The Xenopus Pregnancy Test". British Medical Journal. 2 (4067): 1253–1274.2. doi:10.1136/bmj.2.4067.1253. PMC 2211252. PMID 20781969.
  16. ↑ Diagnosis of Pregnancy, Louis P. Bosman, British Medical Journal 1937;2:939, 6 November 1937
  17. ↑ Nuwer R (16 May 2013). "Doctors Used to Use Live African Frogs As Pregnancy Tests". Smithsonian.com. Retrieved 30 October 2018.
  18. ↑ "The National Xenopus Resource". Marine Biological Laboratory. Retrieved 2022-04-05.
  19. ↑ Karimi K, Fortriede JD, Lotay VS, Burns KA, Wang DZ, Fisher ME, et al. (January 2018). "Xenbase: a genomic, epigenomic and transcriptomic model organism database". Nucleic Acids Research. 46 (D1): D861–D868. doi:10.1093/nar/gkx936. PMC 5753396. PMID 29059324.
  20. ↑ "Xenopus model organism database". Xenbase.org.
  21. ↑ Hardwick LJ, Philpott A (December 2015). "An oncologist׳s friend: How Xenopus contributes to cancer research". Developmental Biology. Modeling Human Development and Disease in Xenopus. 408 (2): 180–187. doi:10.1016/j.ydbio.2015.02.003. PMC 4684227. PMID 25704511.
  22. ↑ Gurdon JB, Lane CD, Woodland HR, Marbaix G (September 1971). "Use of frog eggs and oocytes for the study of messenger RNA and its translation in living cells". Nature. 233 (5316): 177–182. Bibcode:1971Natur.233..177G. doi:10.1038/233177a0. PMID 4939175. S2CID 4160808.
  23. ↑ Reynolds FH, Premkumar E, Pitha PM (December 1975). "Interferon activity produced by translation of human interferon messenger RNA in cell-free ribosomal systems and in Xenopus oöcytes". Proceedings of the National Academy of Sciences of the United States of America. 72 (12): 4881–4885. Bibcode:1975PNAS...72.4881R. doi:10.1073/pnas.72.12.4881. PMC 388836. PMID 1061077.
  24. ↑ Heasman J, Kofron M, Wylie C (June 2000). "Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach". Developmental Biology. 222 (1): 124–134. doi:10.1006/dbio.2000.9720. PMID 10885751.
  25. ↑ Schäfer T, Pütz M, Lienkamp S, Ganner A, Bergbreiter A, Ramachandran H, et al. (December 2008). "Genetic and physical interaction between the NPHP5 and NPHP6 gene products". Human Molecular Genetics. 17 (23): 3655–3662. doi:10.1093/hmg/ddn260. PMC 2802281. PMID 18723859.
  26. ↑ Reversade B, Escande-Beillard N, Dimopoulou A, Fischer B, Chng SC, Li Y, et al. (September 2009). "Mutations in PYCR1 cause cutis laxa with progeroid features". Nature Genetics. 41 (9): 1016–1021. doi:10.1038/ng.413. PMID 19648921. S2CID 10221927.
  27. ↑ Pittman AM, Naranjo S, Webb E, Broderick P, Lips EH, van Wezel T, et al. (June 2009). "The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression". Genome Research. 19 (6): 987–993. doi:10.1101/gr.092668.109. PMC 2694486. PMID 19395656.
  28. ↑ Joukov V, Groen AC, Prokhorova T, Gerson R, White E, Rodriguez A, et al. (November 2006). "The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly". Cell. 127 (3): 539–552. doi:10.1016/j.cell.2006.08.053. PMID 17081976. S2CID 17769149.
  29. ↑ You Z, Bailis JM, Johnson SA, Dilworth SM, Hunter T (November 2007). "Rapid activation of ATM on DNA flanking double-strand breaks". Nature Cell Biology. 9 (11): 1311–1318. doi:10.1038/ncb1651. PMID 17952060. S2CID 17389213.
  30. 1 2 Ben-Yehoyada M, Wang LC, Kozekov ID, Rizzo CJ, Gottesman ME, Gautier J (September 2009). "Checkpoint signaling from a single DNA interstrand crosslink". Molecular Cell. 35 (5): 704–715. doi:10.1016/j.molcel.2009.08.014. PMC 2756577. PMID 19748363.
  31. ↑ Sobeck A, Stone S, Landais I, de Graaf B, Hoatlin ME (September 2009). "The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways". The Journal of Biological Chemistry. 284 (38): 25560–25568. doi:10.1074/jbc.M109.007690. PMC 2757957. PMID 19633289.
  32. ↑ Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, et al. (July 2007). "Non-transcriptional control of DNA replication by c-Myc". Nature. 448 (7152): 445–451. Bibcode:2007Natur.448..445D. doi:10.1038/nature05953. PMID 17597761. S2CID 4422771.
  33. ↑ Dean S, Marchetti R, Kirk K, Matthews KR (May 2009). "A surface transporter family conveys the trypanosome differentiation signal". Nature. 459 (7244): 213–217. Bibcode:2009Natur.459..213D. doi:10.1038/nature07997. PMC 2685892. PMID 19444208.
  34. ↑ Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M, et al. (May 2009). "Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations". The New England Journal of Medicine. 360 (19): 1960–1970. doi:10.1056/NEJMoa0810276. PMC 3398803. PMID 19420365.
  35. ↑ Gustina AS, Trudeau MC (August 2009). "A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channels". Proceedings of the National Academy of Sciences of the United States of America. 106 (31): 13082–13087. Bibcode:2009PNAS..10613082G. doi:10.1073/pnas.0900180106. PMC 2722319. PMID 19651618.
  36. ↑ Duarri A, Teijido O, López-Hernández T, Scheper GC, Barriere H, Boor I, et al. (December 2008). "Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects". Human Molecular Genetics. 17 (23): 3728–3739. doi:10.1093/hmg/ddn269. PMC 2581428. PMID 18757878.
  37. ↑ Blitz IL, Biesinger J, Xie X, Cho KW (December 2013). "Biallelic genome modification in F(0) Xenopus tropicalis embryos using the CRISPR/Cas system". Genesis. 51 (12): 827–834. doi:10.1002/dvg.22719. PMC 4039559. PMID 24123579.
  38. ↑ Nakayama T, Fish MB, Fisher M, Oomen-Hajagos J, Thomsen GH, Grainger RM (December 2013). "Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis". Genesis. 51 (12): 835–843. doi:10.1002/dvg.22720. PMC 3947545. PMID 24123613.
  39. ↑ Wang F, Shi Z, Cui Y, Guo X, Shi YB, Chen Y (2015-04-14). "Targeted gene disruption in Xenopus laevis using CRISPR/Cas9". Cell & Bioscience. 5 (1): 15. doi:10.1186/s13578-015-0006-1. PMC 4403895. PMID 25897376.
  40. ↑ Bhattacharya D, Marfo CA, Li D, Lane M, Khokha MK (December 2015). "CRISPR/Cas9: An inexpensive, efficient loss of function tool to screen human disease genes in Xenopus". Developmental Biology. Modeling Human Development and Disease in Xenopus. 408 (2): 196–204. doi:10.1016/j.ydbio.2015.11.003. PMC 4684459. PMID 26546975.
  41. ↑ Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, et al. (January 2009). "FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination". Cell. 136 (1): 123–135. doi:10.1016/j.cell.2008.10.051. PMID 19135894. S2CID 16458957.
  42. ↑ Cordenonsi M, Montagner M, Adorno M, Zacchigna L, Martello G, Mamidi A, et al. (February 2007). "Integration of TGF-beta and Ras/MAPK signaling through p53 phosphorylation". Science. 315 (5813): 840–843. Bibcode:2007Sci...315..840C. doi:10.1126/science.1135961. PMID 17234915. S2CID 83962686.
  43. ↑ Fuentealba LC, Eivers E, Ikeda A, Hurtado C, Kuroda H, Pera EM, De Robertis EM (November 2007). "Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal". Cell. 131 (5): 980–993. doi:10.1016/j.cell.2007.09.027. PMC 2200633. PMID 18045539.
  44. ↑ Kim NG, Xu C, Gumbiner BM (March 2009). "Identification of targets of the Wnt pathway destruction complex in addition to beta-catenin". Proceedings of the National Academy of Sciences of the United States of America. 106 (13): 5165–5170. Bibcode:2009PNAS..106.5165K. doi:10.1073/pnas.0810185106. PMC 2663984. PMID 19289839.
  45. ↑ Kaláb P, Pralle A, Isacoff EY, Heald R, Weis K (March 2006). "Analysis of a RanGTP-regulated gradient in mitotic somatic cells". Nature. 440 (7084): 697–701. Bibcode:2006Natur.440..697K. doi:10.1038/nature04589. PMID 16572176. S2CID 4398374.
  46. ↑ Tsai MY, Wang S, Heidinger JM, Shumaker DK, Adam SA, Goldman RD, Zheng Y (March 2006). "A mitotic lamin B matrix induced by RanGTP required for spindle assembly". Science. 311 (5769): 1887–1893. Bibcode:2006Sci...311.1887T. doi:10.1126/science.1122771. PMID 16543417. S2CID 12219529.
  47. ↑ Ma L, Tsai MY, Wang S, Lu B, Chen R, Yates JR, et al. (March 2009). "Requirement for Nudel and dynein for assembly of the lamin B spindle matrix". Nature Cell Biology. 11 (3): 247–256. doi:10.1038/ncb1832. PMC 2699591. PMID 19198602.
  48. ↑ Emanuele MJ, Stukenberg PT (September 2007). "Xenopus Cep57 is a novel kinetochore component involved in microtubule attachment". Cell. 130 (5): 893–905. doi:10.1016/j.cell.2007.07.023. PMID 17803911. S2CID 17520550.
  49. 1 2 Noireaux V, Liu AP (June 2020). "The New Age of Cell-Free Biology". Annual Review of Biomedical Engineering. Annual Reviews. 22 (1): 51–77. doi:10.1146/annurev-bioeng-092019-111110. PMID 32151150. S2CID 212652742.
  50. ↑ Akkers RC, van Heeringen SJ, Jacobi UG, Janssen-Megens EM, Françoijs KJ, Stunnenberg HG, Veenstra GJ (September 2009). "A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos". Developmental Cell. 17 (3): 425–434. doi:10.1016/j.devcel.2009.08.005. PMC 2746918. PMID 19758566.
  51. ↑ Hontelez S, van Kruijsbergen I, Georgiou G, van Heeringen SJ, Bogdanovic O, Lister R, Veenstra GJ (December 2015). "Embryonic transcription is controlled by maternally defined chromatin state". Nature Communications. 6: 10148. Bibcode:2015NatCo...610148H. doi:10.1038/ncomms10148. PMC 4703837. PMID 26679111.
  52. ↑ Walker JC, Harland RM (May 2009). "microRNA-24a is required to repress apoptosis in the developing neural retina". Genes & Development. 23 (9): 1046–1051. doi:10.1101/gad.1777709. PMC 2682950. PMID 19372388.
  53. ↑ Rosa A, Spagnoli FM, Brivanlou AH (April 2009). "The miR-430/427/302 family controls mesendodermal fate specification via species-specific target selection". Developmental Cell. 16 (4): 517–527. doi:10.1016/j.devcel.2009.02.007. PMID 19386261.
  54. ↑ Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M, et al. (July 2009). "Telomerase modulates Wnt signalling by association with target gene chromatin". Nature. 460 (7251): 66–72. Bibcode:2009Natur.460...66P. doi:10.1038/nature08137. PMC 4349391. PMID 19571879.
  55. ↑ De Val S, Chi NC, Meadows SM, Minovitsky S, Anderson JP, Harris IS, et al. (December 2008). "Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors". Cell. 135 (6): 1053–1064. doi:10.1016/j.cell.2008.10.049. PMC 2782666. PMID 19070576.
  56. ↑ Li Y, Rankin SA, Sinner D, Kenny AP, Krieg PA, Zorn AM (November 2008). "Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling". Genes & Development. 22 (21): 3050–3063. doi:10.1101/gad.1687308. PMC 2577796. PMID 18981481.
  57. ↑ Carmona-Fontaine C, Matthews HK, Kuriyama S, Moreno M, Dunn GA, Parsons M, et al. (December 2008). "Contact inhibition of locomotion in vivo controls neural crest directional migration". Nature. 456 (7224): 957–961. Bibcode:2008Natur.456..957C. doi:10.1038/nature07441. PMC 2635562. PMID 19078960.
  58. ↑ Buitrago-Delgado E, Nordin K, Rao A, Geary L, LaBonne C (June 2015). "NEURODEVELOPMENT. Shared regulatory programs suggest retention of blastula-stage potential in neural crest cells". Science. 348 (6241): 1332–1335. doi:10.1126/science.aaa3655. PMC 4652794. PMID 25931449.
  59. ↑ Gaiano N, Fishell G (2002). "The role of notch in promoting glial and neural stem cell fates". Annual Review of Neuroscience. Annual Reviews. 25 (1): 471–490. doi:10.1146/annurev.neuro.25.030702.130823. PMID 12052917. S2CID 15691580.
  60. ↑ Tsuji T, Lau E, Chiang GG, Jiang W (December 2008). "The role of Dbf4/Drf1-dependent kinase Cdc7 in DNA-damage checkpoint control". Molecular Cell. 32 (6): 862–869. doi:10.1016/j.molcel.2008.12.005. PMC 4556649. PMID 19111665.
  61. ↑ Xu X, Rochette PJ, Feyissa EA, Su TV, Liu Y (October 2009). "MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication". The EMBO Journal. 28 (19): 3005–3014. doi:10.1038/emboj.2009.235. PMC 2760112. PMID 19696745.
  62. ↑ Räschle M, Knipscheer P, Knipsheer P, Enoiu M, Angelov T, Sun J, et al. (September 2008). "Mechanism of replication-coupled DNA interstrand crosslink repair". Cell. 134 (6): 969–980. doi:10.1016/j.cell.2008.08.030. PMC 2748255. PMID 18805090.
  63. ↑ MacDougall CA, Byun TS, Van C, Yee MC, Cimprich KA (April 2007). "The structural determinants of checkpoint activation". Genes & Development. 21 (8): 898–903. doi:10.1101/gad.1522607. PMC 1847708. PMID 17437996.
  64. ↑ Nutt LK, Buchakjian MR, Gan E, Darbandi R, Yoon SY, Wu JQ, et al. (June 2009). "Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2". Developmental Cell. 16 (6): 856–866. doi:10.1016/j.devcel.2009.04.005. PMC 2698816. PMID 19531356.
  65. ↑ Viczian AS, Solessio EC, Lyou Y, Zuber ME (August 2009). "Generation of functional eyes from pluripotent cells". PLOS Biology. 7 (8): e1000174. doi:10.1371/journal.pbio.1000174. PMC 2716519. PMID 19688031.
  66. ↑ Dzamba BJ, Jakab KR, Marsden M, Schwartz MA, DeSimone DW (March 2009). "Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization". Developmental Cell. 16 (3): 421–432. doi:10.1016/j.devcel.2009.01.008. PMC 2682918. PMID 19289087.
  67. ↑ Beattie MS, Bresnahan JC, Lopate G (October 1990). "Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs". Journal of Neurobiology. 21 (7): 1108–1122. doi:10.1002/neu.480210714. PMID 2258724.
  68. ↑ Park TJ, Mitchell BJ, Abitua PB, Kintner C, Wallingford JB (July 2008). "Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells". Nature Genetics. 40 (7): 871–879. doi:10.1038/ng.104. PMC 2771675. PMID 18552847.
  69. ↑ Mitchell B, Jacobs R, Li J, Chien S, Kintner C (May 2007). "A positive feedback mechanism governs the polarity and motion of motile cilia". Nature. 447 (7140): 97–101. Bibcode:2007Natur.447...97M. doi:10.1038/nature05771. PMID 17450123. S2CID 4415593.
  70. ↑ Kälin RE, Bänziger-Tobler NE, Detmar M, Brändli AW (July 2009). "An in vivo chemical library screen in Xenopus tadpoles reveals novel pathways involved in angiogenesis and lymphangiogenesis". Blood. 114 (5): 1110–1122. doi:10.1182/blood-2009-03-211771. PMC 2721788. PMID 19478043.
  71. ↑ Ny A, Koch M, Vandevelde W, Schneider M, Fischer C, Diez-Juan A, et al. (September 2008). "Role of VEGF-D and VEGFR-3 in developmental lymphangiogenesis, a chemicogenetic study in Xenopus tadpoles". Blood. 112 (5): 1740–1749. doi:10.1182/blood-2007-08-106302. PMID 18474726. S2CID 14663578.
  72. ↑ Cha HJ, Byrom M, Mead PE, Ellington AD, Wallingford JB, Marcotte EM (2012-01-01). "Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent". PLOS Biology. 10 (8): e1001379. doi:10.1371/journal.pbio.1001379. PMC 3423972. PMID 22927795.
  73. ↑ Zimmer C (2012-08-21). "Gene Tests in Yeast Aid Work on Cancer". The New York Times.
  74. ↑ Fini JB, Le Mevel S, Turque N, Palmier K, Zalko D, Cravedi JP, Demeneix BA (August 2007). "An in vivo multiwell-based fluorescent screen for monitoring vertebrate thyroid hormone disruption". Environmental Science & Technology. 41 (16): 5908–5914. Bibcode:2007EnST...41.5908F. doi:10.1021/es0704129. PMID 17874805.
  75. ↑ Dupré A, Boyer-Chatenet L, Sattler RM, Modi AP, Lee JH, Nicolette ML, Kopelovich L, Jasin M, Baer R, Paull TT, Gautier J (February 2008). "A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex". Nature Chemical Biology. 4 (2): 119–25. doi:10.1038/nchembio.63. PMC 3065498. PMID 18176557.
  76. ↑ Landais I, Sobeck A, Stone S, LaChapelle A, Hoatlin ME (February 2009). "A novel cell-free screen identifies a potent inhibitor of the Fanconi anemia pathway". International Journal of Cancer. 124 (4): 783–92. doi:10.1002/ijc.24039. PMID 19048618. S2CID 33589304.
  77. 1 2 Dagle JM, Weeks DL (December 2001). "Oligonucleotide-based strategies to reduce gene expression". Differentiation; Research in Biological Diversity. 69 (2–3): 75–82. doi:10.1046/j.1432-0436.2001.690201.x. PMID 11798068.
  78. 1 2 Blum M, De Robertis EM, Wallingford JB, Niehrs C (October 2015). "Morpholinos: Antisense and Sensibility". Developmental Cell. 35 (2): 145–149. doi:10.1016/j.devcel.2015.09.017. PMID 26506304.
  79. ↑ Rana AA, Collart C, Gilchrist MJ, Smith JC (November 2006). "Defining synphenotype groups in Xenopus tropicalis by use of antisense morpholino oligonucleotides". PLOS Genetics. 2 (11): e193. doi:10.1371/journal.pgen.0020193. PMC 1636699. PMID 17112317.
    "A Xenopus tropicalis antisense morpholino screen". Gurdon Institute. 4 March 2014. Archived from the original on 12 June 2018. Retrieved 17 January 2007.
  80. ↑ Xenbase
  • Xenbase ~ A Xenopus laevis and tropicalis Web Resource
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.