Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish

Yin, Viravuth P.; Thomson, J. Michael; Thummel, Ryan; Hyde, David R.; Hammond, Scott M.; Poss, Kenneth D.

doi:10.1101/gad.1641808

Cited by 146 publications

(167 citation statements)

References 25 publications

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“…The effect was pronounced at 6 days postamputation (dpa), after which the fins began to regenerate over time (data not shown), which is consistent with the half-life of the morpholinos but also indicates that the injections did not irreversibly block regeneration. These results demonstrate that an intact miRNA pathway is essential for regeneration and are consistent with the hypothesis that induction of specific miRNAs is needed for proper regeneration (19).…”

Section: Figsupporting

confidence: 76%

“…miRNAs are a recently discovered class of genes that regulate gene expression at the posttranscriptional level and are required for development, stem cell maintenance, and renewal (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Recently, Yin et al (19) showed that fibroblast growth factor (Fgf) signaling alters the expression of multiple miRNAs during regeneration. One of the miRNA targets of Fgf signaling, miR-133, targets mps1, which encodes a kinase that regulates blastemal proliferation.…”

Section: Lef1 ͉ Mir-203mentioning

confidence: 99%

“…Some miRNAs that change during regeneration did not appear to return to their previous expression levels after 5 weeks at 27°C, possibly due to incomplete regeneration. We hypothesize that miRNAs exhibiting decreased expression during active regeneration enable expression of genes required for regeneration (19), whereas miRNAs that are up-regulated during regeneration repress genes that normally prevent proliferation and/or maintain terminal cell differentiation.…”

Section: Lef1 ͉ Mir-203mentioning

confidence: 99%

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Regulation of zebrafish fin regeneration by microRNAs

Thatcher

Paydar²,

Anderson³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

109

104

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A number of genes have been implicated in regeneration, but the regulation of these genes, particularly pertaining to regeneration in higher vertebrates, remains an interesting and mostly open question. We have studied microRNA (miRNA) regulation of regeneration and found that an intact miRNA pathway is essential for caudal fin regeneration in zebrafish. We also showed that miR-203 directly targets the Wnt signaling transcription factor Lef1 during this process. Repression of Lef1 by miR-203 blocks regeneration, whereas loss of miR-203 results in excess Lef1 levels and fin overgrowth. Expression of Lef1 from mRNAs lacking 3 UTR recognition elements can rescue the effects of excess miR-203, demonstrating that these effects are due to specific regulation of lef1 by miR-203. Our data support a model in which regulation of Lef1 protein levels by miR-203 is a key limiting step during regeneration.M ost vertebrates, including humans, are unable to regenerate the majority of lost or damaged tissues. In contrast, zebrafish are able to regenerate various damaged tissues, including fins, hearts, retinas, and spinal cords (1). For fins, regeneration relies on the formation of blastema cells, stem cell-like cells that either are recruited to the damaged area or originate from the de-differentiation of cells in the area (2, 3). Zebrafish caudal fins undergo isometric growth (i.e., fin grows in proportion to body size) throughout life, and understanding the regulatory mechanisms for controlling such growth remains a key question. The fin is composed of multiple bony rays that grow autonomously and are made up of bony segments, termed lepidotrichia. Each ray is composed of two hemirays, which create a protective shell around nerves, blood vessels, and mesenchymal cells. Fins grow through the addition of bone to the distal tip of the fin. Regeneration proceeds through at least five steps: wound healing, mesenchymal disorganization or reorganization, blastema formation, outgrowth, and termination (1, 4). miRNAs are a recently discovered class of genes that regulate gene expression at the posttranscriptional level and are required for development, stem cell maintenance, and renewal (5-18). Recently, Yin et al. (19) showed that fibroblast growth factor (Fgf) signaling alters the expression of multiple miRNAs during regeneration. One of the miRNA targets of Fgf signaling, miR-133, targets mps1, which encodes a kinase that regulates blastemal proliferation. Interestingly, these authors also found that various other markers of regeneration were indirectly activated on the reduction of miR-133 levels, suggesting that overall regulation of regeneration by miRNAs might be quite complex. Here we show that an intact miRNA pathway indeed is essential for regeneration. Furthermore, we show that in addition to regulation of Fgf signaling during regeneration, Wnt signaling also subject is to miRNA regulation through miR-203 control of Lef1.To examine global miRNA expression patterns in regenerating fins, we first conducted microarrays. Cauda...

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Section: Figsupporting

confidence: 76%

Section: Lef1 ͉ Mir-203mentioning

confidence: 99%

Section: Lef1 ͉ Mir-203mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of zebrafish fin regeneration by microRNAs

Thatcher

Paydar²,

Anderson³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

109

104

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show abstract

“…In zebrafish, the caudal fin regenerates by means of an epimorphic process similar to that of amphibian limbs, including the formation of a blastema (Poss et al, 2003), and involving many of the same signaling molecules, including Fgf20 (Whitehead et al, 2005;Stoick-Cooper et al, 2007a). In a recent study, Yin et al (2008) describe several miRNAs that are differentially expressed between normal and Fgf inhibited zebrafish tails. One of these, miR-133, is dramatically down-regulated during caudal fin regeneration, but high in normal tails.…”

Section: Micrornasmentioning

confidence: 99%

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

Beck

Belmonte

Christen

2009

Developmental Dynamics

150

139

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While Xenopus is a well-known model system for early vertebrate development, in recent years, it has also emerged as a leading model for regeneration research. As an anuran amphibian, Xenopus laevis can regenerate the larval tail and limb by means of the formation of a proliferating blastema, the lens of the eye by transdifferentiation of nearby tissues, and also exhibits a partial regeneration of the postmetamorphic froglet forelimb. With the availability of inducible transgenic techniques for Xenopus, recent experiments are beginning to address the functional role of genes in the process of regeneration. The use of soluble inhibitors has also been very successful in this model. Using the more traditional advantages of Xenopus, others are providing important lineage data on the origin of the cells that make up the tissues of the regenerate. Finally, transcriptome analyses of regenerating tissues seek to identify the genes and cellular processes that enable successful regeneration.

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“…Genes and cell-signaling pathways that are involved in zebrafish fin regeneration have been previously characterized (Laforest et al, 1998;Tawk et al, 2000;Quint et al, 2002;Padhi et al, 2004;Smith et al, 2006;Jazwinska et al, 2007;Stoick-Cooper et al, 2007a, b;Wills et al, 2008;Yin et al, 2008;Chablais and Jazwinska, 2010). For example, Whitehead et al (2005) reported that the expression of fgf20a, a gene that encodes a member of the fibroblast growth factor family, plays important roles in the initiation of fin regeneration, and that decreases in fgf20a expression result in inhibition of fin regeneration.…”

Section: Introductionmentioning

confidence: 99%

Tissue regeneration after injury in adult zebrafish: The regenerative potential of the caudal fin

Chen

Cui

et al. 2011

Developmental Dynamics

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The zebrafish has the potential to regenerate many of its tissues. In this study, we examined caudal fin regeneration in zebrafish that received repeated injuries (fin amputation) at different ages. In zebrafish that received repeated injuries, the potential for caudal fin regeneration, such as tissue growth and the expression of regeneration marker genes (msxb, fgf20a, bmp2b), did not decline in comparison to zebrafish that received only one amputation surgery. The process of initial fin regeneration (e.g., tissue outgrowth and the expression of regeneration marker genes at 7 days post-amputation) did not seem to correlate with age. However, slight differences in fin outgrowth were observed between young and old animals when examined in the late regeneration stages (e.g., 20 and 30 days post-amputation). Together, the data suggest that zebrafish has unlimited regenerative potential in the injured caudal fin. Developmental Dynamics 240:1271-1277,

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Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish

Cited by 146 publications

References 25 publications

Regulation of zebrafish fin regeneration by microRNAs

Regulation of zebrafish fin regeneration by microRNAs

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

Tissue regeneration after injury in adult zebrafish: The regenerative potential of the caudal fin

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