Old questions, new tools, and some answers to the mystery of fin regeneration

Akimenko, Marie‐Andrée; Marí‐Beffa, Manuel; Becerra, José; Géraudie, Jacqueline

doi:10.1002/dvdy.10248

Cited by 276 publications

(286 citation statements)

References 73 publications

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“…We suspect that both genetic and epigenetic cues may play a role (see Akimenko et al, 1995Akimenko et al, , 2003Makino et al, 2005;Bouzaffour et al, 2009). It is possible that fin regeneration (at least the initial events) is regulated by activation of a genetic program, which may result in unlimited production of blastema cells.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…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)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Lef1 ͉ Mir-203mentioning

confidence: 99%

Regulation of zebrafish fin regeneration by microRNAs

Thatcher

Paydar²,

Anderson³

et al. 2008

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

108

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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“…While there is widespread interest in regeneration (Akimenko et al, 2003;Poss et al, 2003), especially given the recent emphasis on stem cell research, functional understanding of the regeneration process remains limited (Akimenko et al, 2003;. Recently, zebrafish caudal fin regeneration has emerged as an ideal model to further our understanding of vertebrate regeneration due to the simpler anatomical structure of the caudal fin as compared to the urodele limb .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of zebrafish fin regeneration using in vivo electroporation of morpholinos against fgfr1 and msxb

Thummel

Bai

Sarras

et al. 2005

Developmental Dynamics

128

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Increased interest in using zebrafish as a model organism has led to a resurgence of fin regeneration studies. This has allowed for the identification of a large number of gene families, including signaling molecules and transcription factors, which are expressed during regeneration. However, in cases where no specific inhibitor is available for the gene product of interest, determination of a functional role for these genes has been difficult. Here we demonstrate that in vivo electroporation of morpholino oligonucleotides is a feasible approach for protein knock-down during fin regeneration. Morpholino oligonucleotides against fgfr1 and msxb were utilized and knock-down of both proteins resulted in reduced fin outgrowth. Importantly, Fgfr1 knock-down phenocopied outgrowth inhibition obtained with an Fgfr1 inhibitor. Furthermore, this method provided direct evidence for a functional role for msxb in caudal fin regeneration. Finally, knock-down of Fgfr1, but not Msxb, affected the blastemal expression of msxc, suggesting this technique can be used to determine epistasis in genetic pathways affecting regeneration. Thus, this convenient reverse genetic approach allows researchers to quickly (1) assess the function of genes known to be expressed during fin regeneration, (2) screen genes for functional relevance during fin regeneration, and (3) assign genes to the molecular pathways underlying fin regeneration. Developmental Dynamics 235:336 -346, 2006.

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Old questions, new tools, and some answers to the mystery of fin regeneration

Cited by 276 publications

References 73 publications

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

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

Regulation of zebrafish fin regeneration by microRNAs

Inhibition of zebrafish fin regeneration using in vivo electroporation of morpholinos against fgfr1 and msxb

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