Alexander James Hale, Ali Kiai, Jelte Sikkens, Jeroen den Hertog
{"title":"肿瘤抑制因子 Pten 缺失的斑马鱼尾鳍褶再生能力受损","authors":"Alexander James Hale, Ali Kiai, Jelte Sikkens, Jeroen den Hertog","doi":"10.1002/reg2.88","DOIUrl":null,"url":null,"abstract":"<p><p>Zebrafish are able to completely regrow their caudal fin-folds after amputation. Following injury, wound healing occurs, followed by the formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. Here we show that, surprisingly, the phosphatase and tumor suppressor Pten, an antagonist of phosphoinositide-3-kinase (PI3K) signaling, is required for zebrafish caudal fin-fold regeneration. We found that homozygous knock-out mutant (<i>ptena<sup>-/-</sup>ptenb<sup>-/-</sup></i> ) zebrafish embryos, lacking functional Pten, did not regenerate their caudal fin-folds. AKT phosphorylation was enhanced, which is consistent with the function of Pten. Reexpression of Pten, but not catalytically inactive mutant Pten-C124S, rescued regeneration, as did pharmacological inhibition of PI3K. Blastema formation, determined by in situ hybridization for the blastema marker <i>junbb</i>, appeared normal upon caudal fin-fold amputation of <i>ptena<sup>-/-</sup>ptenb<sup>-/-</sup></i> zebrafish embryos. Whole-mount immunohistochemistry using specific markers indicated that proliferation was arrested in embryos lacking functional Pten, and that apoptosis was enhanced. Together, these results suggest a critical role for Pten by limiting PI3K signaling during the regenerative outgrowth phase of zebrafish caudal fin-fold regeneration.</p>","PeriodicalId":90316,"journal":{"name":"Regeneration (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2017-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743786/pdf/","citationCount":"0","resultStr":"{\"title\":\"Impaired caudal fin-fold regeneration in zebrafish deficient for the tumor suppressor Pten.\",\"authors\":\"Alexander James Hale, Ali Kiai, Jelte Sikkens, Jeroen den Hertog\",\"doi\":\"10.1002/reg2.88\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Zebrafish are able to completely regrow their caudal fin-folds after amputation. Following injury, wound healing occurs, followed by the formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. Here we show that, surprisingly, the phosphatase and tumor suppressor Pten, an antagonist of phosphoinositide-3-kinase (PI3K) signaling, is required for zebrafish caudal fin-fold regeneration. We found that homozygous knock-out mutant (<i>ptena<sup>-/-</sup>ptenb<sup>-/-</sup></i> ) zebrafish embryos, lacking functional Pten, did not regenerate their caudal fin-folds. AKT phosphorylation was enhanced, which is consistent with the function of Pten. Reexpression of Pten, but not catalytically inactive mutant Pten-C124S, rescued regeneration, as did pharmacological inhibition of PI3K. Blastema formation, determined by in situ hybridization for the blastema marker <i>junbb</i>, appeared normal upon caudal fin-fold amputation of <i>ptena<sup>-/-</sup>ptenb<sup>-/-</sup></i> zebrafish embryos. Whole-mount immunohistochemistry using specific markers indicated that proliferation was arrested in embryos lacking functional Pten, and that apoptosis was enhanced. Together, these results suggest a critical role for Pten by limiting PI3K signaling during the regenerative outgrowth phase of zebrafish caudal fin-fold regeneration.</p>\",\"PeriodicalId\":90316,\"journal\":{\"name\":\"Regeneration (Oxford, England)\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-11-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743786/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Regeneration (Oxford, England)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/reg2.88\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2017/8/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regeneration (Oxford, England)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/reg2.88","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/8/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
Impaired caudal fin-fold regeneration in zebrafish deficient for the tumor suppressor Pten.
Zebrafish are able to completely regrow their caudal fin-folds after amputation. Following injury, wound healing occurs, followed by the formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. Here we show that, surprisingly, the phosphatase and tumor suppressor Pten, an antagonist of phosphoinositide-3-kinase (PI3K) signaling, is required for zebrafish caudal fin-fold regeneration. We found that homozygous knock-out mutant (ptena-/-ptenb-/- ) zebrafish embryos, lacking functional Pten, did not regenerate their caudal fin-folds. AKT phosphorylation was enhanced, which is consistent with the function of Pten. Reexpression of Pten, but not catalytically inactive mutant Pten-C124S, rescued regeneration, as did pharmacological inhibition of PI3K. Blastema formation, determined by in situ hybridization for the blastema marker junbb, appeared normal upon caudal fin-fold amputation of ptena-/-ptenb-/- zebrafish embryos. Whole-mount immunohistochemistry using specific markers indicated that proliferation was arrested in embryos lacking functional Pten, and that apoptosis was enhanced. Together, these results suggest a critical role for Pten by limiting PI3K signaling during the regenerative outgrowth phase of zebrafish caudal fin-fold regeneration.