首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb.
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The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb.

机译:RNaseIII酶Dicer是形态发生所必需的,而不是脊椎动物四肢的模式。

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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.
机译:据信,含有RNaseIII的酶Dicer对于大多数(如果不是全部)microRNA(miRNA)的加工以及将长dsRNA加工成小的干扰RNA都是必需的。由于Dicer在斑马鱼和小鼠中的完全丧失会导致早期的胚胎致死性,因此无法确定Dicer在构图发育中的脊椎动物胚胎中的后期组织中起什么作用(如果有的话)。为了绕开Dicer的早期开发需求,我们在小鼠中创建了该基因的条件等位基因。使用转基因驱动肢体中胚层的离散区域中的Cre表达,我们发现去除切块机会导致加工的miRNA丢失。从表型上看,发育迟缓部分是由于大量细胞死亡以及特定基因表达失调导致的,其形成的肢体要小得多。因此,Dicer是正常小鼠肢体形成所必需的。令人惊讶的是,我们没有发现Dicer缺陷肢芽的基本模式或组织特异性分化方面的缺陷。

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