The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb
The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb
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DOI：
10.1073/pnas.0504834102
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发表时间：
2005-08-02
影响因子：
11.1
通讯作者：
Tabin, CJ
中科院分区：
文献类型：
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作者：
Harfe, BD;McManus, MT;Tabin, CJ
含有RNaseIII的酶Dicer被认为是加工大多数（如果不是全部）microRNA（miRNA）和将长dsRNA加工成小干扰RNA所必需的。由于斑马鱼和小鼠中Dicer的完全丧失导致早期胚胎死亡，因此不可能确定Dicer在发育中的脊椎动物胚胎中形成后期组织的模式中的作用（如果有的话）。为了绕过发育中对Dicer的早期需求，我们在小鼠中创建了该基因的条件等位基因。使用转基因驱动Cre表达在肢体中胚层的离散区域，我们发现，去除切丁酶导致加工的miRNA的损失。从表型上看，部分由于大量细胞死亡以及特定基因表达失调导致的发育迟缓导致了肢体的形成。因此，Dicer是正常小鼠肢体形成所必需的。然而，引人注目的是，我们没有检测到缺陷的基本图案或组织特异性分化的Dicer缺陷肢芽。
The RNaseIII-containing enzyme Dicer is believed to be required for the processing of most, if not all, microRNAs (miRNAs) and for processing long dsRNA into small interfering RNAs. Because the complete loss of Dicer in both zebrafish and mice results in early embryonic lethality, it has been impossible to determine what role, if any, Dicer has in patterning later tissues in the developing vertebrate embryo. To bypass the early requirement of Dicer in development, we have created a conditional allele of this gene in mice. Using transgenes to drive Cre expression in discrete regions of the limb mesoderm, we find that removal of Dicer results in the loss of processed miRNAs. Phenotypically, developmental delays, in part due to massive cell death as well as disregulation of specific gene expression, lead to the formation of a much smaller limb. Thus, Dicer is required for the formation of normal mouse limbs. Strikingly, however, we did not detect defects in basic patterning or in tissue-specific differentiation of Dicer-deficient limb buds.