A subunit of the mediator complex regulates vertebrate neuronal development
A subunit of the mediator complex regulates vertebrate neuronal development
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DOI：
10.1073/pnas.0605414103
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发表时间：
2006-11-14
影响因子：
11.1
通讯作者：
Guo, Su
中科院分区：
文献类型：
--
作者：
Wang, Xiaoqun;Yang, Nan;Guo, Su
基因表达的独特特征决定了不同的细胞身份。这些配置文件是如何在开发过程中建立的尚不清楚。在这里，我们报告了在斑马鱼中发现的影响神经元发育突变的突变不动(Mot)，显示出单胺能神经元和颅感觉神经节的缺陷，而泛神经元标记Hu的表达在很大程度上没有受到干扰；GABA能和脑运动神经元的亚群似乎并不缺乏。位置克隆揭示了MOT编码MED12，MED12是进化上保守的介体复合体的一个组成部分，其在脊椎动物中的体内功能尚不清楚。MOT/MED12转录本在胚胎大脑中丰富，似乎与另外两个中介成分Med17和Med21不同。将人的MED12 RNA导入斑马鱼可以恢复mot突变体的正常状态，并显著地导致WT区神经元过早分化和单胺能神经元亚型的增加。进一步的研究表明，MOT/MED12对调控不同的神经元决定基因的表达是必要的，并且当过表达时能够增加，包括Zash 1a和LIM 1，并在这一过程中充当SOX 9的体内辅助因子。总之，我们的分析揭示了Mot/MED12在脊椎动物神经元发育中的调节作用。
The unique profiles of gene expression dictate distinct cellular identity. How these profiles are established during development is not clear. Here we report that the mutant motionless (mot), identified in a genetic screen for mutations that affect neuronal development in zebrafish, displays deficits of monoaminergic neurons and cranial sensory ganglia, whereas expression of the panneuronal marker Hu is largely unperturbed; GABAergic and subsets of cranial motor neurons do not appear to be deficient. Positional cloning reveals that mot encodes Med12, a component of the evolutionarily conserved Mediator complex, whose in vivo function is not well understood in vertebrates. mot/med12 transcripts are enriched in the embryonic brain and appear distinct from two other Mediator components Med17 and Med21. Delivery of human med12 RNA into zebrafish restores normality to the mot mutant and, strikingly, leads to premature neuronal differentiation and an increased production of monoaminergic neuronal subtypes in WT. Further investigation reveals that mot/med12 is necessary to regulate, and when overexpressed is capable of increasing, the expression of distinct neuronal determination genes, including zash 1a and lim 1, and serves as an in vivo cofactor for Sox 9 in this process. Together, our analyses reveal a regulatory role of Mot/ Med12 in vertebrate neuronal development.