Regulation of zebrafish fin regeneration by microRNAs

被引:95
作者
Thatcher, Elizabeth J. [1 ]
Paydar, Ima [1 ]
Anderson, Kimberly K. [1 ]
Patton, James G. [1 ]
机构
[1] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA
关键词
lef1; miR-203;
D O I
10.1073/pnas.0803713105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Writ 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.
引用
收藏
页码:18384 / 18389
页数:6
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