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Regenerative capacity in newts is not altered by repeated regeneration and ageing

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      Abstract

      The extent to which adult newts retain regenerative capability remains one of the greatest unanswered questions in the regeneration field. Here we report a long-term lens regeneration project spanning 16 years that was undertaken to address this question. Over that time, the lens was removed 18 times from the same animals, and by the time of the last tissue collection, specimens were at least 30 years old. Regenerated lens tissues number 18 and number 17, from the last and the second to the last extraction, respectively, were analysed structurally and in terms of gene expression. Both exhibited structural properties identical to lenses from younger animals that had never experienced lens regeneration. Expression of mRNAs encoding key lens structural proteins or transcription factors was very similar to that of controls. Thus, contrary to the belief that regeneration becomes less efficient with time or repetition, repeated regeneration, even at old age, does not alter newt regenerative capacity.

      Abstract

      Tissue regeneration is of great interest; however the number of times a given tissue can regenerate is unknown. Now, Eguchi et al. demonstrate that the lens of the Japanese newt—Cynops pyrrhogaster—can regenerate 18 times over a 16-year period, and that the new lenses are similar to those of control adult animals.

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      Most cited references 4

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      Transdifferentiation.

       R. Kodama,  G Eguchi (1993)
      Recent progress in studies of development and differentiation has greatly stimulated analysis of transdifferentiation, and more cell types capable of transdifferentiation have been documented. Growth factors must be essential, key factors in the regulation of the transdifferentiation process, in cooperation with components of the extracellular matrix, which helps to stabilize the differentiated state of tissues. Trials to induce transdifferentiation artificially by transfection of genes have also begun.
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        Regeneration according to Spallanzani.

        In this report, we elaborate on a letter that Spallanzani wrote to Bonnet reporting his findings on regeneration in worms, snails, tadpoles, and salamanders. The letter (original in French and translated in English; see Supplementary Material, which is available online) was written to discuss whether or not regeneration in these animals supports Bonnet's theory on germs. The letter includes several drawings by Spallanzani, which were not published in the Prodromo, his book on Animal Reproduction. Spallanzani made important observations, which he described with considerable detail, but overall he was unable to confidently support Bonnet's theory. This letter reflects the way of thinking in the 18(th) century that shaped the important scientific fields of regeneration and reproduction. 2009 Wiley-Liss, Inc.
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          Carcinogens on regeneration. Effects of N-methyl-N'-nitro-N-nitrosoguanidine and 4-nitroquinoline-1-oxide on limb regeneration in adult newts.

          A microcrystal (ca 5 micrograms) of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 4-nitroquinoline-1-oxide (4NQO) was directly administered to the regeneration blastema on day 7 after amputation of a forelimb in the newt in order to analyze the effect of such potent carcinogenic substances on regeneration cells. Although neither MNNG nor 4NQO arrested regeneration completely, they caused great retardation of the regeneration cone formation followed by various abnormalities in the bony structures. Abnormal regenerants could be classified into the following four categories; (1) complete absence of both ulna and radius; (2) subregeneration or superregeneration of carpals and digits; (3) multiple disorganization of skeletal elements; (4) arrest of regeneration at the stage of regeneration cone. The polarity of regenerants developed after application of MNNG or 4NQO was very often shifted, during which the regeneration cone was always formed from the site where a microcrystal of the carcinogens was administered. The secondary regeneration initiated by reamputation of the regenerating limb, which had received the carcinogens at the early blastema stage, proceeded in the same way as observed in the case of a simple amputation. This suggested local and temporal effects of the carcinogens applied. Nevertheless, tumor formation has not induced in the newt limb so far. We can learn from these data that both MNNG and 4NQO only alter behavior of the newt regeneration cells without excreting their carcinogenic effects on them, and that the newt cells are highly resistant and stable against the above-mentioned carcinogens.
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            Author and article information

            Affiliations
            [1 ]simpleNational Institute for Basic Biology, National Institutes of Natural Sciences , Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan.
            [2 ]simpleDepartment of Biology and Center for Tissue Regeneration and Engineering, University of Dayton , Dayton, Ohio 45469-2320, USA.
            [3 ]simpleSanford Children's Health Research Center, The Sanford-Burnham Medical Research Institute , La Jolla, California 92037, USA.
            [4 ]Present address: simpleShokei Educational Institution , Kuhonji 2-6-78, Kumamoto 862-8678, Japan.
            [5 ]Deceased.
            Journal
            Nat Commun
            Nature Communications
            Nature Publishing Group
            2041-1723
            July 2011
            12 July 2011
            : 2
            : 384
            3144589
            ncomms1389
            10.1038/ncomms1389
            21750538
            Copyright © 2011, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

            This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

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