Wnt1-cre-mediated Conditional Loss of Dicer Results in Malformation of the Midbrain and Cerebellum and Failure of Neural Crest and Dopaminergic Differentiation in Mice
Wnt1-cre-mediated Conditional Loss of Dicer Results in Malformation of the Midbrain and Cerebellum and Failure of Neural Crest and Dopaminergic Differentiation in Mice
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Wnt1-cre 介导的 Dicer 条件性缺失导致小鼠中脑和小脑畸形以及神经嵴和多巴胺能分化失败
DOI：
10.1093/jmcb/mjq008
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发表时间：
2010-06-01
影响因子：
5.5
通讯作者：
Cheng, Leping
中科院分区：
文献类型：
--
作者：
Huang, Tianwen;Liu, Yueguang;Cheng, Leping
microRNAs（miRNAs）参与神经嵴（NC）细胞的发育和其他神经元分化的机制仍知之甚少。在这里，我们调查的整体功能的miRNAs在胚胎发育中，通过检查Wnt 1-cre介导的Dicer基因敲除小鼠。Dicer消融导致中脑和小脑畸形以及NC和多巴胺能分化失败。首先，Dicer突变体胎儿表现出顶盖和小脑的严重畸形，眼睑张开。第二，Dicer突变小鼠中源自颅NC的骨骼结构丢失或大部分消融。第三，NC细胞中Dicer基因的缺失导致背根神经节、肠神经系统和交感神经节的畸形。有趣的是，神经肽Y及其潜在调节因子TrkA、AP-2 α和AP-2 β的表达在Dicer突变小鼠的交感神经元中基本上被消除。第四，原位杂交数据显示，miR-9、miR-124和miR-218在Dicer突变小鼠中脑和嘴侧后脑区的表达大部分被消除。然后，我们证明了多巴胺能神经元的发育受损Dicer删除小鼠。因此，我们的研究表明，miRNAs有助于胚胎发育在多个位置。
The involvement of microRNAs (miRNAs) in the development of the neural crest (NC) cells and other neuronal differentiation is still poorly understood. Here, we investigated the global function of miRNAs in embryonic development by examining the Wnt1-cre-mediated Dicer knockout mice. Dicer ablation resulted in malformation of the midbrain and cerebellum and failure of NC and dopaminergic differentiation. First, the Dicer mutant fetuses exhibited dramatic malformation of the tectum and cerebellum and the eyelids were open. Second, the skeletal structures that are derived from the cranial NC were lost or mostly ablated in Dicer mutant mice. Third, deletion of Dicer in the NC cells resulted in the malformation of the dorsal root ganglia, enteric nervous system and sympathetic ganglia. Interestingly, the expression of neuropeptide Y and its potential regulators TrkA, AP-2 alpha and AP-2 beta was largely abolished in sympathetic neurons of Dicer mutant mice. Fourth, in situ hybridization data revealed that the expression of miR-9, miR-124 and miR-218 in the midbrain and rostral hindbrain area was mostly eliminated in the Dicer mutant mice. We then demonstrated that the development of dopaminergic neurons was impaired in Dicer-deleted mice. Our studies therefore suggest that miRNAs contribute to the embryonic development in multiple locations.