PUBLICATION

Regulation of zebrafish fin regeneration by microRNAs

Authors
Thatcher, E.J., Paydar, I., Anderson, K.K., and Patton, J.G.
ID
ZDB-PUB-081121-22
Date
2008
Source
Proceedings of the National Academy of Sciences of the United States of America   105(47): 18384-18389 (Journal)
Registered Authors
Patton, James G., Thatcher, Elizabeth
Keywords
lef1, miR-203
MeSH Terms
  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • DNA Primers
  • Fluorescent Antibody Technique
  • MicroRNAs/genetics
  • MicroRNAs/physiology*
  • Regeneration/genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors/genetics
  • Transcription Factors/physiology
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
PubMed
19015519 Full text @ Proc. Natl. Acad. Sci. USA
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping