A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans
A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans
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DOI：
10.1038/nature02255
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发表时间：
2003-12-18
期刊：
影响因子：
64.8
通讯作者：
Hobert, O
中科院分区：
文献类型：
--
作者：
Johnston, RJ;Hobert, O
左/右功能不对称是如何在解剖学上对称的神经系统之上分层的，人们对此知之甚少。在线虫秀丽隐杆线虫中，两种形态学上的双侧味觉感受器神经元，ASE左（ASEL）和ASE右（ASER），显示出与化学感受特异性多样化相关的推定化学感受器基因的左/右不对称表达模式（1，2）。在这里，我们表明，以前未定义的microRNA称为lsy-6控制这种神经元的左/右不对称的化学感受受体的表达。我们从神经元左/右不对称缺陷的遗传筛选中检索的lsy-6突变体显示ASEL特异性化学受体表达谱的损失，同时获得ASER特异性谱。Alsy-6报告基因构建体在包括ASEL在内的不到10个神经元中表达，但不表达ASER。lsy-6通过抑制cog-1对ASEL发挥作用，cog-1是一种Nkx型同源框基因，在其非翻译区含有lsy-6互补位点，并已显示控制ASE特异性化学受体表达谱（3）。lsy-6是我们所知的第一个在神经元模式中发挥作用的microRNA，为左/右轴的形成提供了新的见解。
How left/right functional asymmetry is layered on top of an anatomically symmetrical nervous system is poorly understood. In the nematode Caenorhabditis elegans, two morphologically bilateral taste receptor neurons, ASE left (ASEL) and ASE right (ASER), display a left/right asymmetrical expression pattern of putative chemoreceptor genes that correlates with a diversification of chemosensory specificities(1,2). Here we show that a previously undefined microRNA termed lsy-6 controls this neuronal left/right asymmetry of chemosensory receptor expression. lsy-6 mutants that we retrieved from a genetic screen for defects in neuronal left/right asymmetry display a loss of the ASEL-specific chemoreceptor expression profile with a concomitant gain of the ASER-specific profile. Alsy-6 reporter gene construct is expressed in less than ten neurons including ASEL, but not ASER. lsy-6 exerts its effects on ASEL through repression of cog-1, an Nkx-type homeobox gene, which contains a lsy-6 complementary site in its 30 untranslated region and that has been shown to control ASE-specific chemoreceptor expression profiles(3). lsy-6 is the first microRNA to our knowledge with a role in neuronal patterning, providing new insights into left/right axis formation.