OpenLB
Open Library of Bioscience
Advanced Search
Proceedings of the National Academy of Sciences of the United States of America
Nov 25, 2008;105 (47): 18384-9.

Regulation of zebrafish fin regeneration by microRNAs.

Elizabeth J Thatcher, Ima Paydar, Kimberly K Anderson, James G Patton
Author Information
  1. Elizabeth J Thatcher: Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235-1634, USA.
PMID: 19015519 DOI: 10.1073/pnas.0803713105

Abstract

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.

References

  1. Science. 2002 Dec 13;298(5601):2188-90 [PMID: 12481136]
  2. Nucleic Acids Res. 2004 Jan 1;32(Database issue):D109-11 [PMID: 14681370]
  3. Dev Dyn. 2000 Oct;219(2):282-6 [PMID: 11002347]
  4. Dev Dyn. 2006 Feb;235(2):336-46 [PMID: 16273523]
  5. Cell. 2006 Mar 10;124(5):877-81 [PMID: 16530032]
  6. Nature. 2008 Sep 4;455(7209):58-63 [PMID: 18668040]
  7. Curr Biol. 2007 Aug 21;17(16):1390-5 [PMID: 17683938]
  8. Genes Dev. 2008 Mar 15;22(6):728-33 [PMID: 18347091]
  9. Science. 2005 May 6;308(5723):833-8 [PMID: 15774722]
  10. Genes Dev. 2005 Jun 1;19(11):1288-93 [PMID: 15937218]
  11. Nature. 2001 Jan 18;409(6818):363-6 [PMID: 11201747]
  12. Curr Biol. 2007 Mar 20;17(6):533-8 [PMID: 17320391]
  13. Cell. 2006 Mar 24;124(6):1169-81 [PMID: 16564011]
  14. Nat Rev Genet. 2004 May;5(5):396-400 [PMID: 15143321]
  15. Curr Opin Genet Dev. 2006 Apr;16(2):203-8 [PMID: 16503132]
  16. Genetics. 1995 Dec;141(4):1583-95 [PMID: 8601496]
  17. Dev Dyn. 2003 Feb;226(2):190-201 [PMID: 12557198]
  18. Nature. 2000 Feb 24;403(6772):901-6 [PMID: 10706289]
  19. Nat Cell Biol. 2006 Mar;8(3):278-84 [PMID: 16489342]
  20. Mech Dev. 1999 Aug;86(1-2):147-50 [PMID: 10446273]
  21. Genes Dev. 1994 Jun 1;8(11):1311-23 [PMID: 7926732]
  22. Nature. 2000 Nov 2;408(6808):86-9 [PMID: 11081512]
  23. Development. 2007 Feb;134(3):479-89 [PMID: 17185322]
  24. Cell. 1993 Dec 3;75(5):843-54 [PMID: 8252621]
  25. Genes Dev. 2007 Jun 1;21(11):1292-315 [PMID: 17545465]
  26. Nature. 2008 Mar 13;452(7184):225-9 [PMID: 18311128]
  27. Development. 2002 Nov;129(22):5141-9 [PMID: 12399306]
  28. Dev Dyn. 2007 Aug;236(8):2172-80 [PMID: 17584857]
  29. Nature. 2005 Jun 9;435(7043):839-43 [PMID: 15944709]
  30. PLoS Biol. 2007 Aug;5(8):e203 [PMID: 17676975]
  31. FEBS Lett. 2005 Oct 31;579(26):5911-22 [PMID: 16111679]
  32. Cell Death Differ. 2008 Jul;15(7):1187-95 [PMID: 18483491]
  33. Nature. 2005 Jun 16;435(7044):974-8 [PMID: 15944714]
  34. Nat Genet. 2007 Feb;39(2):259-63 [PMID: 17220889]
  35. Nat Genet. 2003 Nov;35(3):215-7 [PMID: 14528307]
  36. ScientificWorldJournal. 2006 Jun 02;6 Suppl 1:38-54 [PMID: 17205186]
  37. Nat Genet. 2003 Nov;35(3):217-8 [PMID: 14528306]
  38. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14599-604 [PMID: 16204379]
  39. Genome Res. 2004 Dec;14(12):2486-94 [PMID: 15574827]
  40. Nature. 2008 Sep 4;455(7209):64-71 [PMID: 18668037]
  41. Genes Dev. 2005 Feb 15;19(4):489-501 [PMID: 15713842]
  42. Trends Biochem Sci. 2004 Sep;29(9):462-8 [PMID: 15337119]

Grants

  1. T32 GM062758/NIGMS NIH HHS
  2. GM62758/NIGMS NIH HHS
  3. T32 GM008554/NIGMS NIH HHS
  4. R01 GM075790/NIGMS NIH HHS
  5. GM 075790/NIGMS NIH HHS

MeSH Term

3' Untranslated Regions
Animals
Base Sequence
Blotting, Northern
Blotting, Western
DNA Primers
Fluorescent Antibody Technique
MicroRNAs
Regeneration
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors
Zebrafish
Zebrafish Proteins

Chemicals

3' Untranslated Regions
DNA Primers
LEF1 protein, zebrafish
MicroRNAs
Transcription Factors
Zebrafish Proteins
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 3

Word Cloud

Created with Highcharts 10.0.0regenerationmiR-203Lef1regulationfingenesmiRNAzebrafishexcesslevelseffectsnumberimplicatedparticularlypertaininghighervertebratesremainsinterestingmostlyopenquestionstudiedmicroRNAfoundintactpathwayessentialcaudalalsoshoweddirectlytargetsWntsignalingtranscriptionfactorprocessRepressionblockswhereaslossresultsovergrowthExpressionmRNAslacking3'UTRrecognitionelementscanrescuedemonstratingduespecificlef1datasupportmodelproteinkeylimitingstepRegulationmicroRNAs

Similar Articles

Cited By