Targeted deletion of Dicer disrupts lens morphogenesis, corneal epithelium stratification, and whole eye development.

Targeted deletion of Dicer disrupts lens morphogenesis, corneal epithelium stratification, and whole eye development.
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DOI:
10.1002/dvdy.22056
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发表时间:
2009-09
影响因子:
2.5
通讯作者:
Piatigorsky, Joram
Piatigorsky, Joram
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Yan;Piatigorsky, Joram

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Dicer是一种对miRNA加工至关重要的核糖核酸酶,在发育中的小鼠角膜和晶状体中大量表达。我们通过有条件地删除小鼠晶状体和角膜上皮中的Dicer基因,研究了Dicer和miRNAs在眼睛发育中的作用。成年Dicer条件null (DicerCN)小鼠有严重的小眼症,没有可识别的晶状体和角膜上皮分层不良。靶向删除Dicer可有效抑制胚胎发生12.5天时晶状体发育中的miRNA加工(E12.5)。晶状体发育开始正常,但在E14.5和E18.5之间发生进行性营养不良。微阵列分析显示,在E13.5时,DicerCN晶状体中P53信号被激活,与E12.5和E14.5之间细胞凋亡增加和细胞增殖减少一致。Pax6及其他晶状体发育转录因子的表达在E12.5和E14.5间无明显变化,但随着晶状体退化而降低。我们的数据表明Dicer和mirna在晶状体和角膜发育中起着不可或缺的作用。
Dicer, a ribonuclease essential for miRNA processing, is expressed abundantly in developing mouse cornea and lens. We studied the roles of Dicer and miRNAs in eye development by conditionally deleting the Dicer gene in the mouse lens and corneal epithelium. Adult Dicer conditional null (DicerCN) mice had severe microphthalmia with no discernible lens and a poorly stratified corneal epithelium. Targeted deletion of Dicer effectively inhibited miRNA processing in the developing lens at 12.5 day of embryogenesis (E12.5). Lens development initiated normally but underwent progressive dystrophy between E14.5 and E18.5. Microarray analysis revealed activation of P53 signaling in DicerCN lenses at E13.5, consistent with increased apoptosis and reduced cell proliferation between E12.5 and E14.5. Expression of Pax6 and other lens developmental transcription factors were not greatly affected between E12.5 and E14.5 but decreased as the lens degenerated. Our data indicated an indispensible role for Dicer and miRNAs in lens and corneal development.
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