{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:50:56Z","timestamp":1762102256294,"version":"3.37.3"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In contrast to amniotes (reptiles, birds and mammals), anamniotes (fishes and amphibians) can effectively regenerate body appendages such as fins, limbs and tails. Why such a useful capability was progressively lost in amniotes remains unknown. As we have hypothesized recently, one of the reasons for this could be loss of some genes regulating the regeneration in evolution of amniotes. Here, we demonstrate the validity of this hypothesis by showing that genes of small GTPases <jats:italic>Ras-dva1<\/jats:italic> and <jats:italic>Ras-dva<\/jats:italic>2, that had been lost in a stepwise manner during evolution of amniotes and disappeared completely in placental mammals, are important for regeneration in anamniotes. Both <jats:italic>Ras-dva<\/jats:italic> genes are quickly activated in regenerative wound epithelium and blastema forming in the amputated adult <jats:italic>Danio rerio<\/jats:italic> fins and <jats:italic>Xenopus laevis<\/jats:italic> tadpoles\u2019 tails and hindlimb buds. Down-regulation of any of two <jats:italic>Ras-dva<\/jats:italic> genes in fish and frog resulted in a retardation of regeneration accompanied by down-regulation of the regeneration marker genes. On the other hand, <jats:italic>Ras-dva<\/jats:italic> over-expression in tadpoles\u2019 tails restores regeneration capacity during the refractory period when regeneration is blocked due to natural reasons. Thus our data on Ras-dva genes, which were eliminated in amniotes but play role in anamniotes regeneration regulation, satisfy our hypothesis.<\/jats:p>","DOI":"10.1038\/s41598-018-30811-0","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T11:49:39Z","timestamp":1535024979000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Ras-dva small GTPases lost during evolution of amniotes regulate regeneration in anamniotes"],"prefix":"10.1038","volume":"8","author":[{"given":"Anastasiya S.","family":"Ivanova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7098-0962","authenticated-orcid":false,"given":"Daria D.","family":"Korotkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina V.","family":"Ermakova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia Yu.","family":"Martynova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey G.","family":"Zaraisky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria B.","family":"Tereshina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"30811_CR1","first-page":"13","volume":"27","author":"DL Stocum","year":"1984","unstructured":"Stocum, D. L. The urodele limb regeneration blastema. Determination and organization of the morphogenetic field. Differentiation. 27, 13\u201328 (1984).","journal-title":"Determination and organization of the morphogenetic field. Differentiation."},{"key":"30811_CR2","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1006\/dbio.1997.8732","volume":"192","author":"B Christen","year":"1997","unstructured":"Christen, B. & Slack, J. M. W. FGF-8 is associated with anteroposterior patterning and limb regeneration in Xenopus. Dev. Biol. 192, 455\u2013466 (1997).","journal-title":"Dev. Biol."},{"key":"30811_CR3","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/S1534-5807(03)00233-8","volume":"5","author":"CW Beck","year":"2003","unstructured":"Beck, C. W., Christen, B. & Slack, J. M. W. Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate. Dev. Cell 5, 429\u2013439 (2003).","journal-title":"Dev. Cell"},{"key":"30811_CR4","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1126\/science.1117637","volume":"310","author":"GG Whitehead","year":"2005","unstructured":"Whitehead, G. G., Makino, S., Lien, C.-L. & Keating, M. T. Fgf20 Is Essential for Initiating Zebrafish Fin Regeneration. Science 310, 1957\u20131960 (2005).","journal-title":"Science"},{"key":"30811_CR5","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.ydbio.2008.01.032","volume":"316","author":"G Lin","year":"2008","unstructured":"Lin, G. & Slack, J. M. W. Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration. Dev. Biol. 316, 323\u2013335 (2008).","journal-title":"Dev. Biol."},{"key":"30811_CR6","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1242\/dev.043885","volume":"137","author":"F Chablais","year":"2010","unstructured":"Chablais, F. & Jazwinska, A. IGF signaling between blastema and wound epidermis is required for fin regeneration. Development 137, 871\u2013879 (2010).","journal-title":"Development"},{"key":"30811_CR7","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/j.semcdb.2012.09.013","volume":"23","author":"P Murawala","year":"2012","unstructured":"Murawala, P., Tanaka, E. M. & Currie, J. D. Regeneration: The ultimate example of wound healing. Semin. Cell Dev. Biol. 23, 954\u2013962 (2012).","journal-title":"Semin. Cell Dev. Biol."},{"key":"30811_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/srep08123","volume":"5","author":"AS Ivanova","year":"2015","unstructured":"Ivanova, A. S. et al. The secreted factor Ag1 missing in higher vertebrates regulates fins regeneration in Danio rerio. Sci. Rep. 5, 8123 (2015).","journal-title":"Sci. Rep."},{"key":"30811_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/srep01279","volume":"3","author":"AS Ivanova","year":"2013","unstructured":"Ivanova, A. S., Tereshina, M. B., Ermakova, G. V., Belousov, V. V. & Zaraisky, A. G. Agr genes, missing in amniotes, are involved in the body appendages regeneration in frog tadpoles. Sci. Rep. 3, 1279 (2013).","journal-title":"Sci. Rep."},{"key":"30811_CR10","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1126\/science.1147710","volume":"318","author":"A Kumar","year":"2007","unstructured":"Kumar, A., Godwin, J. W., Gates, P. B., Garza-Garcia, A. A. & Brockes, J. P. Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate. Science 318, 772\u20137 (2007).","journal-title":"Science"},{"key":"30811_CR11","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1242\/dev.02207","volume":"133","author":"MB Tereshina","year":"2006","unstructured":"Tereshina, M. B., Zaraisky, A. G. & Novoselov, V. V. Ras-dva, a member of novel family of small GTPases, is required for the anterior ectoderm patterning in the Xenopus laevis embryo. Development 133, 485\u201394 (2006).","journal-title":"Development"},{"key":"30811_CR12","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S1567-133X(02)00077-7","volume":"3","author":"VV Novoselov","year":"2003","unstructured":"Novoselov, V. V., Alexandrova, E. M., Ermakova, G. V. & Zaraisky, A. G. Expression zones of three novel genes abut the developing anterior neural plate of Xenopus embryo. Gene Expr. Patterns 3, 225\u2013230 (2003).","journal-title":"Gene Expr. Patterns"},{"key":"30811_CR13","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1242\/bio.20147401","volume":"3","author":"MB Tereshina","year":"2014","unstructured":"Tereshina, M. B., Ermakova, G. V., Ivanova, A. S. & Zaraisky, A. G. Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis embryos by controlling Fgf8 and Agr signaling at the anterior border of the neural plate. Biol. Open 3, 192\u2013203 (2014).","journal-title":"Biol. Open"},{"key":"30811_CR14","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.gep.2010.10.009","volume":"11","author":"MB Tereshina","year":"2011","unstructured":"Tereshina, M. B., Bayramov, A. V. & Zaraisky, A. G. Expression patterns of genes encoding small GTPases Ras-dva-1 and Ras-dva-2 in the Xenopus laevis tadpoles. Gene Expr. Patterns 11, 156\u2013161 (2011).","journal-title":"Gene Expr. Patterns"},{"key":"30811_CR15","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1002\/dvdy.21890","volume":"238","author":"CW Beck","year":"2009","unstructured":"Beck, C. W., Belmonte, J. C. I. & Christen, B. Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms. Dev. Dyn. 238, 1226\u20131248 (2009).","journal-title":"Dev. Dyn."},{"key":"30811_CR16","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1006\/dbio.2001.0180","volume":"233","author":"H Yokoyama","year":"2001","unstructured":"Yokoyama, H., Ide, H. & Tamura, K. FGF-10 Stimulates Limb Regeneration Ability in Xenopus laevis. Dev. Biol. 233, 72\u201379 (2001).","journal-title":"Dev. Biol."},{"key":"30811_CR17","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1101\/gad.1540507","volume":"21","author":"CL Stoick-Cooper","year":"2007","unstructured":"Stoick-Cooper, C. L., Moon, R. T. & Weidinger, G. Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine. Genes Dev. 21, 1292\u20131315 (2007).","journal-title":"Genes Dev."},{"key":"30811_CR18","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ydbio.2006.10.048","volume":"301","author":"A-S Tseng","year":"2007","unstructured":"Tseng, A.-S., Adams, D. S., Qiu, D., Koustubhan, P. & Levin, M. Apoptosis is required during early stages of tail regeneration in Xenopus laevis. Dev. Biol. 301, 62\u201369 (2007).","journal-title":"Dev. Biol."},{"key":"30811_CR19","first-page":"574","volume":"33","author":"MB Tereshina","year":"2007","unstructured":"Tereshina, M. B., Belousov, V. V. & Zaraiskii, A. G. Study of the mechanism of Ras-dva small GTPase intracellular localization. Bioorganicheskaia khimiia 33, 574\u2013576 (2007).","journal-title":"Bioorganicheskaia khimiia"},{"key":"30811_CR20","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.zool.2014.12.003","volume":"118","author":"AP Russell","year":"2015","unstructured":"Russell, A. P., Lynn, S. E., Powell, G. L. & Cottle, A. The regenerated tail of juvenile leopard geckos (Gekkota: Eublepharidae: Eublepharis macularius) preferentially stores more fat than the original. Zoology 118, 183\u2013191 (2015).","journal-title":"Zoology"},{"key":"30811_CR21","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1002\/jmor.20422","volume":"276","author":"MK Vickaryous","year":"2015","unstructured":"Vickaryous, M. K., Meldrum, G. & Russell, A. P. Armored geckos: A histological investigation of osteoderm development in Tarentola (Phyllodactylidae) and Gekko (Gekkonidae) with comments on their regeneration and inferred function. J. Morphol. 276, 1345\u20131357 (2015).","journal-title":"J. Morphol."},{"key":"30811_CR22","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1139\/z81-007","volume":"59","author":"SR Scadding","year":"1981","unstructured":"Scadding, S. R. Limb regeneration in adult amphibia. Can. J. Zool. 59, 34\u201346 (1981).","journal-title":"Can. J. Zool."},{"key":"30811_CR23","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.celrep.2016.12.063","volume":"18","author":"DM Bryant","year":"2017","unstructured":"Bryant, D. M. et al. A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors. Cell Rep. 18, 762\u2013776 (2017).","journal-title":"Cell Rep."},{"key":"30811_CR24","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/S0925-4773(02)00199-5","volume":"117","author":"I Bachy","year":"2002","unstructured":"Bachy, I., Berthon, J. & R\u00e9taux, S. Defining pallial and subpallial divisions in the developing Xenopus forebrain. Mech. Dev. 117, 163\u2013172 (2002).","journal-title":"Mech. Dev."},{"key":"30811_CR25","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/S0091-679X(08)60307-6","volume":"36","author":"RM Harland","year":"1991","unstructured":"Harland, R. M. In situ hybridization: an improved whole-mount method for Xenopus embryos. Methods Cell Biol. 36, 685\u201395 (1991).","journal-title":"Methods Cell Biol."},{"key":"30811_CR26","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.ydbio.2007.03.524","volume":"307","author":"GV Ermakova","year":"2007","unstructured":"Ermakova, G. V., Solovieva, E. A., Martynova, N. Y. & Zaraisky, A. G. The homeodomain factor Xanf represses expression of genes in the presumptive rostral forebrain that specify more caudal brain regions. Dev. Biol. 307, 483\u2013497 (2007).","journal-title":"Dev. Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30811-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30811-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30811-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T08:52:08Z","timestamp":1671612728000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30811-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,29]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["30811"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-30811-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2018,8,29]]},"assertion":[{"value":"29 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"13035"}}