Apoptosis of limb innervating motor neurons and erosion of motor pool identity upon lineage specific Dicer inactivation
Apoptosis of limb innervating motor neurons and erosion of motor pool identity upon lineage specific Dicer inactivation
复制标题
DOI：
10.3389/fnins.2012.00069
复制
发表时间：
2012-01-01
影响因子：
4.3
通讯作者：
Wichterle, Hynek
中科院分区：
文献类型：
--
作者：
Chen, Jun-An;Wichterle, Hynek
哺乳动物脊髓运动神经元分化为数百种亚型，对于维持身体姿势和协调复杂运动至关重要。运动神经元的分化是由外在信号控制的，这些外在信号调节内在的遗传程序，指定和巩固运动神经元亚型的身份。虽然转录因子已被认为是内在程序的主要调节因子，但转录后调节的作用尚未得到系统的测试。由Dicer介导的RNA发夹切割产生的microRNA通过转录后沉默促进基因调控。在这里，我们使用Olig 2-cre条件删除Dicer基因的运动神经元祖细胞，以检查有丝分裂后脊髓运动神经元的miRNA生物合成中断的影响。我们报告说，尽管最初的运动神经元祖细胞的数量增加，Dicer功能的中断导致许多肢体和交感神经节支配脊髓运动神经元的损失。此外，它还导致了车辆调配场标识规范的缺陷。因此，我们的研究结果表明，miRNA是控制运动神经元存活和获得亚型特异性特性的遗传程序的组成部分。
Diversification of mammalian spinal motor neurons into hundreds of subtypes is critical for the maintenance of body posture and coordination of complex movements. Motor neuron differentiation is controlled by extrinsic signals that regulate intrinsic genetic programs specifying and consolidating motor neuron subtype identity. While transcription factors have been recognized as principal regulators of the intrinsic program, the role of posttranscriptional regulations has not been systematically tested. MicroRNAs produced by Dicer mediated cleavage of RNA hairpins contribute to gene regulation by posttranscriptional silencing. Here we used Olig2-cre conditional deletion of Dicer gene in motor neuron progenitors to examine effects of miRNA biogenesis disruption on postmitotic spinal motor neurons. We report that despite the initial increase in the number of motor neuron progenitors, disruption of Dicer function results in a loss of many limb- and sympathetic ganglia-innervating spinal motor neurons. Furthermore, it leads to defects in motor pool identity specification. Thus, our results indicate that miRNAs are an integral part of the genetic program controlling motor neuron survival and acquisition of subtype specific properties.