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

National Institute for Basic Biology, National Institutes of Natural Sciences, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan.
Nature Communications (Impact Factor: 11.47). 07/2011; 2(1):384. DOI: 10.1038/ncomms1389
Source: PubMed


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.

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    • "These patterns suggest that regenerative ability is associated with age-related changes in cells that form tissues and organs, as well as maturation of systems that broadly regulate development and physiology (Seifert and Voss, 2013). Exceptions include lens regeneration in adult newts (Eguchi et al., 2011) and fin regeneration in zebrafish (Itou et al., 2012). "
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    ABSTRACT: Mexican axolotls lose potential for lens regeneration two weeks after hatching. We used microarrays to identify differently expressed genes before and after this critical time, using RNA isolated from iris. Over 3700 genes were identified as differentially expressed in response to lentectomy between young (seven days post hatching) and old (three-months post hatching) axolotl larvae. Strikingly, many of the genes were only expressed in the early or late iris. Genes that were highly expressed in young iris significantly enriched electron transport chain, transcription, metabolism, and cell cycle gene ontologies, all of which are associated with lens regeneration. In contrast, genes associated with cellular differentiation and tissue maturation were uniquely expressed in old iris. Many of these expression differences strongly suggest that young and old iris samples were collected before and after the spleen became developmentally competent to produce and secrete cells with humoral and innate immunity functions. Our study establishes the axolotl as a powerful model to investigate age-related cellular differentiation and immune system ontogeny within the context of tissue regeneration.This article is protected by copyright. All rights reserved.
    06/2014; 1(3). DOI:10.1002/reg2.25
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    • "Normally developed out of the epidermis at the embryonic stage, the lens re-emerges in a stepwise fashion from the edge of the iris instead (Henry and Tsonis 2010). Neither age nor repeated amputation seems to diminish this regenerative capability (Eguchi et al. 2011). But it turns out that an injection of the growth factor, FGF2, is all it takes to trigger the onset of development (Hayashi et al. 2004), along with the subsequent expression of other genes. "
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    ABSTRACT: In developmental and evolutionary biology, particular emphasis has been given to the relationship between transcription factors and the cognate cis-regulatory elements of their target genes. These constitute the gene regulatory networks that control expression and are assumed to causally determine the formation of structures and body plans. Comparative analysis has, however, established a broad sequence homology among species that nonetheless display quite different anatomies. Transgenic experiments have also confirmed that many developmentally important elements are, in fact, functionally interchangeable. Although dependent upon the appropriate degree of gene expression, the actual construction of specific structures appears not directly linked to the functions of gene products alone. Instead, the self-formation of complex patterns, due in large part to epigenetic and non-genetic determinants, remains a persisting theme in the study of ontogeny and regenerative medicine. Recent evidence indeed points to the existence of a self-organizing process, operating through a set of intrinsic rules and forces, which imposes coordination and a holistic order upon cells and tissue. This has been repeatedly demonstrated in experiments on regeneration as well as in the autonomous formation of structures in vitro. The process cannot be wholly attributed to the functional outcome of protein-protein interactions or to concentration gradients of diffusible chemicals. This phenomenon is examined here along with some of the methodological and theoretical approaches that are now used in understanding the causal basis for self-organization in development and its evolution.
    Theory in Biosciences 04/2014; 133(3-4). DOI:10.1007/s12064-014-0200-4 · 1.23 Impact Factor
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    • "In both anurans and urodeles, body size and limb size rapidly increase following metamorphosis ; thus comparisons between pre-and post-metamorphic animals are inherently confounded by size effects. Lastly, as it relates to studies in older urodeles, aging itself (either cellular or physiological) may affect regeneration rate and ability, although this relationship is at present poorly understood (Lund et al. 2009; Anchelin et al. 2011; Eguchi et al. 2011; Nachtrab et al. 2011; Itou et al. 2012; Suetsugu-Maki et al. 2012; Seifert and Voss 2013). With the interaction of so many factors, disentangling the effects of any one property with respect to regenerative ability becomes difficult. "
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    ABSTRACT: While most tetrapods are unable to regenerate severed body parts, amphibians display a remarkable ability to regenerate an array of structures. Frogs can regenerate appendages as larva, but they lose this ability around metamorphosis. In contrast, salamanders regenerate appendages as larva, juveniles, and adults. However, the extent to which fundamental traits (e.g., metamorphosis, body size, aging, etc.) restrict regenerative ability remains contentious. Here we utilize the ability of normally paedomorphic adult axolotls (Ambystoma mexicanum) to undergo induced metamorphosis by thyroxine exposure to test how metamorphosis and body size affects regeneration in age-matched paedomorphic and metamorphic individuals. We show that body size does not affect regeneration in adult axolotls, but metamorphosis causes a 2-fold reduction in regeneration rate, and carpal and digit malformations. Furthermore, we find evidence that metamorphic cells may take longer to traverse the cell cycle and display a lower proliferative rate. This study identifies the axolotl as a powerful system to study how metamorphosis restricts regeneration independently of developmental stage, body size, and age; and more broadly how metamorphosis affects tissue-specific changes. This article is protected by copyright. All rights reserved.
    02/2014; 1(1). DOI:10.1002/reg2.8
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