Dicer inactivation stimulates limb regeneration ability in <i>Xenopus laevis</i>

Zhang, Mengshi; Yang, Li; Yuan, Feng; Chen, Ying; Lin, Gufa

doi:10.1111/wrr.12619

Cited by 2 publications

(2 citation statements)

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“…Microinjection and electroporation in the tadpoles were performed as described ( Zhang et al, 2018b ) and also illustrated in Supplementary Figure S3 . Briefly, animals of selected stages were anesthetized with 0.02% MS-222 (Sigma-Aldrich) and injected with control or evi5 Mo, evi5 mRNA, or pcDNA3- GFP DNA plasmid, immediately followed by electroporation, with a platinum Tweezertrodes electrodes (BTX, United States) attached to an ECM 830 square wave generator (BTX, United States).…”

Section: Methodsmentioning

confidence: 99%

Evi5 is required for Xenopus limb and tail regeneration

Yang

Chen

Liu

et al. 2022

Front. Cell Dev. Biol.

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Amphibians such as salamanders and the African clawed frog Xenopus are great models for regeneration studies because they can fully regenerate their lost organs. While axolotl can regenerate damaged organs throughout its lifetime, Xenopus has a limited regeneration capacity after metamorphosis. The ecotropic viral integrative factor 5 (Evi5) is of great interest because its expression is highly upregulated in the limb blastema of axolotls, but remains unchanged in the fibroblastema of post-metamorphic frogs. Yet, its role in regeneration-competent contexts in Xenopus has not been fully analyzed. Here we show that Evi5 is upregulated in Xenopus tadpoles after limb and tail amputation, as in axolotls. Down-regulation of Evi5 with morpholino antisense oligos (Mo) impairs limb development and limb blastema formation in Xenopus tadpoles. Mechanistically, we show that Evi5 knockdown significantly reduces proliferation of limb blastema cells and causes apoptosis, blocking the formation of regeneration blastema. RNA-sequencing analysis reveals that in addition to reduced PDGFα and TGFβ signaling pathways that are required for regeneration, evi5 Mo downregulates lysine demethylases Kdm6b and Kdm7a. And knockdown of Kdm6b or Kdm7a causes defective limb regeneration. Evi5 knockdown also impedes tail regeneration in Xenopus tadpoles and axolotl larvae, suggesting a conserved function of Evi5 in appendage regeneration. Thus, our results demonstrate that Evi5 plays a critical role in appendage regeneration in amphibians.

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Section: Methodsmentioning

confidence: 99%

Evi5 is required for Xenopus limb and tail regeneration

Yang

Chen

Liu

et al. 2022

Front. Cell Dev. Biol.

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“…In addition to the above phenotypes, several other pathways were shown to induce limb regeneration including manipulation of Dicer, 119 the NF-kB pathway, 68 and the melanocortin 4 receptor (Mc4r), pathway. 120 However, it remains unclear if these perturbations might be resulting in dysregulation of the immune system, altering intrinsic abilities or changing environmental cues that favour regeneration.…”

Section: Introductionmentioning

confidence: 99%

To regenerate or not to regenerate: Vertebrate model organisms of regeneration‐competency and ‐incompetency

Aztekin

Storer

2022

Wound Repair Regeneration

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Why only certain species can regenerate their appendages (e.g. tails and limbs) remains one of the biggest mysteries of nature. Unlike anuran tadpoles and salamanders, humans and other mammals cannot regenerate their limbs, but can only regrow lost digit tips under specific circumstances. Numerous hypotheses have been postulated to explain regeneration-incompetency in mammals. By studying model organisms that show varying regenerative abilities, we now have more opportunities to uncover what contributes to regeneration-incompetency and functionally test which perturbations restore appendage regrowth. Particularly, Xenopus laevis tail and limb, and mouse digit tip model systems exhibit naturally occurring variations in regenerative capacities. Here, we discuss major hypotheses that are suggested to contribute to regeneration-incompetency, and how species with varying regenerative abilities reflect on these hypotheses. | INTRODUCTIONAppendage regeneration has fascinated biologists for centuries, 1 as uncovering the molecular and cellular players regulating this process holds potential for therapies aimed at regenerating human limbs. While there are many different model organisms (e.g. zebrafish, salamander, deer) and appendage regeneration models (e.g. tail, digit tip, antler), each with unique characteristics, the bulk of our understanding of appendage regeneration has been derived from studies investigating amphibian limb and tail regeneration. 2 Amputations of appendages in these animals induce certain lineages to show a morphologically identified dedifferentiation phenotype and co-currently a simple wound epidermis covers the amputation plane. 3,4 This simple wound epithelium progresses into becoming a specialised wound epithelium called the apical-epithelial-cap (AEC). The AEC then functions as the key signalling centre during regeneration enabling expansion of lineage-restricted stem and progenitor populations, that are collectively termed the blastema. [5][6][7][8] The continuous interaction between the AEC and the blastema restores the lost appendage. Meanwhile, amputation of the mammalian limb fails to form an AEC or a blastema, and instead results in fibrotic scar formation and regenerative failure. 9Although mice, and in general amniotes including chickens 10 and lizards, 11 cannot perform limb regeneration, mouse digit tip amputations result in regrowth through formation of a blastema. 12,13 Interestingly, unlike limb regeneration in amphibians, there is no reported evidence that an AEC forms during digit tip regeneration, although the wound epidermis is suggested to be important for digit tip regrowth. 7 Instead of a signalling center AEC, nail bed stem cells were proposed to act as a signalling center population enabling expansion of progenitor cells during digit tip regeneration. 14,15 Nonetheless, it remains unclear why mammals, and amniotes in general, cannot perform full limb regeneration.

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Dicer inactivation stimulates limb regeneration ability in Xenopus laevis

Cited by 2 publications

References 39 publications

Evi5 is required for Xenopus limb and tail regeneration

Evi5 is required for Xenopus limb and tail regeneration

To regenerate or not to regenerate: Vertebrate model organisms of regeneration‐competency and ‐incompetency

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