Induction of lef1 during zebrafish fin regeneration

Poss, Kenneth D.; Shen, Jinglai; Keating, Mark T.

doi:10.1002/1097-0177(2000)9999:9999<::aid-dvdy1045>3.3.co;2-3

Cited by 136 publications

(116 citation statements)

References 31 publications

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“…miR-203 was found to be significantly downregulated during regeneration and is predicted to target lef1 (Table 1), a Wnt signaling-regulated transcription factor, the transcription of which is induced during regeneration and serves as a marker of the basal epidermal layer during blastema formation (22). The 3Ј UTR of lef1 contains two potential miRNA recognition elements (MREs) for miR-203 ( Fig.…”

Section: Figmentioning

confidence: 84%

“…Similarly, miR-203 is down-regulated during regeneration and is predicted to target lef1. Regeneration requires up-regulation of lef1 in newly formed regenerative epithelia and can be used as a marker for the initiation of regeneration (21)(22)(23). Thus, significant downregulation of miR-203 during regeneration is consistent with the up-regulation of lef1 that occurs during active regeneration.…”

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: Figmentioning

confidence: 84%

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.

109

104

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“…While amphibians have long been the central characters employed in studies on tissue or organ regeneration (Brockes, 1997;Beck et al, 2009;Contreras et al, 2009;Kragl et al, 2009;Calve et al, 2010), the zebrafish (Danio rerio) have recently emerged as a new vertebrate model for genetic studies of tissue/ organ regeneration. Like amphibians, zebrafish exhibit an enhanced capability of regenerating adult tissues, which include retina, spinal cord, kidney, heart, and fin (Poss et al, 2000a(Poss et al, ,b, 2002aNechiporuk and Keating, 2002;Nechiporuk et al, 2003;Jazwinska et al, 2007;Schoenebeck et al, 2007;Tsai et al, 2007;Qin et al, 2009;Jopling et al, 2010;Thummel et al, 2010). Fin regeneration is a particularly efficient model for studying tissue 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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“…During fin regeneration, a large number of genes, including signalling molecules and transcription factors, are expressed with the end of restoring loss and damaged parts (Poss et al, 2000a;Nechiporuk and Keating, 2002). Laforest et al (1998) analysed the expression of genes involved in the pathway of signalling SHH (Sonic Hedgehog) and observed that shh, ptc and bmp2 are expressed during the fin regeneration in a coordinated way, suggesting the function of these genes in the interaction epidermisblastema, which leads to the synthesis and to the restoration of the ray.…”

Section: Discussionmentioning

confidence: 99%

“…Fin regeneration is characterised by: formation of a multilayered wound epidermis, disorganisation and distal migration of mesenchymal cells proximal to the amputation plane, proliferation of these mesenchymal cells to form the regeneration blastema, continued distal blastemal proliferation to facilitate outgrowth and proximal blastemal differentiation to replace missing structures (Goss and Stagg, 1957;Santamaria and Becerra, 1991;Johnson and Weston, 1995;Poss et al, 2000aPoss et al, , 2000b.…”

Section: Introductionmentioning

confidence: 99%

Influence of indomethacin on the regenerative process of the tail fin of teleost: morphometric and ultrastructural analysis

2010

Braz. J. Biol.

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When partially amputated or severely injured, teleost fins suffer a regenerative process called epimorphic regeneration characterised by the following stages: the formation of a multistratified epidermal layer, the disorganisation and distal migration of multipotent mesenchymal cells, the proliferation of these cells in order to form the blastema, continuous proliferation of distal blastema to facilitate the growth, and differentiation of the proximal blastema in order to restore its lost structure. The regeneration of the fin is extremely sensitive to the action of some drugs that can interfere in its structure restoration. For this reason, and also based on papers relating that indomethacin can interfere somehow in the tissue restoration of many different organisms, the aim of this work is to evaluate the possible effects of this drug in three different doses in the regeneration of the teleost fish tail fin, taking into consideration the synthesis, the disposition and organisation of lepidotrichial matrix components, the restoration of actinotrichia, as well as the fin area itself. Therefore, histochemical, ultrastructural and morphometric analysis were done and it was observed that indomethacin in doses of 20 and 30 mg.L -1 caused a delay in the regenerative process of the dermal skeleton (lepidotrichia and actinotrichia) of the tail fins. These doses could have interfered, momentarily, in the process of blastemal cell differentiation in the cells responsible for the synthesis and disposition of actinotrichia and lepidotrichia or, even interfered in the signalling necessary for the recent differentiated cells to begin synthesising the components of the dermal skeleton. Keywords: indomethacin, regeneration, fin, fish.Influência da indometacina no processo regenerativo da nadadeira caudal de teleósteo: análise morfométrica e ultraestrutural ResumoQuando parcialmente amputadas ou severamente injuriadas, as nadadeiras de teleósteos sofrem um processo de regeneração chamado de regeneração epimórfica, caracterizado pelas seguintes fases: formação de uma capa epidermal multiestratificada, desorganização e migração distal de células mesenquimais multipotentes, proliferação dessas células para formar o blastema, proliferação contínua do blastema distal para facilitar o crescimento e diferenciação do blastema proximal para restaurar as estruturas perdidas. A regeneração que a nadadeira sofre é extremamente sensível à ação de algumas drogas que podem interferir na reparação de suas estruturas. Em vista disso, e também pelo fato de que há relatos na literatura de que a indometacina pode interferir de alguma maneira na restauração tecidual de diversos organismos, o objetivo deste trabalho foi o de avaliar os possíveis efeitos desta droga, em três doses diferentes, na regeneração da nadadeira caudal de peixe teleósteo, considerando a síntese, deposição e organização dos componentes da matriz lepidotriquial, a regeneração da actinotriquia, bem como a área da nadadeira como um todo. Para isso, foram feitas análises h...

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Induction of lef1 during zebrafish fin regeneration

Cited by 136 publications

References 31 publications

Regulation of zebrafish fin regeneration by microRNAs

Regulation of zebrafish fin regeneration by microRNAs

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

Influence of indomethacin on the regenerative process of the tail fin of teleost: morphometric and ultrastructural analysis

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