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首页> 外文期刊>Cell and Tissue Research >Regulation of gene expression during early neuronal differentiation: evidence for patterns conserved across neuron populations and vertebrate classes
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Regulation of gene expression during early neuronal differentiation: evidence for patterns conserved across neuron populations and vertebrate classes

机译：早期神经元分化过程中基因表达的调节：跨神经元种群和脊椎动物类别的保守模式的证据

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Analysis of transcription factor function during neurogenesis has provided a huge amount of data on the generation and specification of diverse neuron populations in the central and peripheral nervous systems of vertebrates. However, an understanding of the induction of key neuron functions including electrical information processing and synaptic transmission lags seriously behind. Whereas pan-neuronal markers such as neurofilaments, neuron-specific tubulin and RNA-binding proteins have often been included in developmental analysis, the molecular players underlying electrical activity and transmitter release have been neglected in studies addressing gene expression during neuronal induction. Here, I summarize the evidence for a distinct accumulation pattern of mRNAs for synaptic proteins, a pattern that is delayed compared with pan-neuronal gene expression during neurogenesis. The conservation of this pattern across diverse avian and mammalian neuron populations suggests a common mechanism for the regulation of various sets of neuronal genes during initial neuronal differentiation. The co-regulation of genes coding for synaptic proteins from embryonic to postnatal development indicates that the expression of the players required for synaptic transmission shares common regulatory features. For the ion channels involved in neuronal electrical activity, such as voltage-gated sodium channels, the situation is less clear because of the lack of comparative studies early during neurogenesis. Transcription factors have been characterized that regulate the expression of synaptic proteins in vitro and in vivo. They currently do not explain the co-regulation of these genes across different neuron populations. The neuron-restrictive silencing factor NRSF/REST targets a large gene set, but not all of the genes coding for pan-neuronal, synaptic and ion channel proteins. The discrepancy between NRSF/REST loss-of-function and silencer-to-activator-switch studies leaves the full functional implications of this factor open. Together with microRNAs, splicing regulators, chromatin remodellers and an increasing list of transcriptional regulators, the factor is embedded in feedback circuits with the potential to orchestrate neuronal differentiation. The precise regulation of the coordinated expression of proteins underlying key neuronal functions by these circuits during neuronal induction is a major emerging topic.
机译：对神经发生过程中转录因子功能的分析已提供了大量有关脊椎动物中枢神经系统和外周神经系统中不同神经元种群的产生和规格的数据。但是，对关键神经元功能的诱导（包括电信息处理和突触传递）的理解严重滞后。发育分析中通常包含泛神经标志物，如神经丝，神经元特异性微管蛋白和RNA结合蛋白，而在研究神经元诱导过程中基因表达的研究中，忽略了电活动和递质释放的分子机制。在这里，我总结了突触蛋白mRNA的独特积累模式的证据，这种模式与神经发生过程中泛神经元基因表达相比被延迟了。在不同的鸟类和哺乳动物神经元群体中这种模式的保守性提示了在初始神经元分化过程中调节各种神经元基因集的共同机制。编码突触蛋白从胚胎到出生后发育的基因的共调控表明，突触传递所需的球员的表达共有共同的监管特征。对于涉及神经元电活动的离子通道，例如电压门控钠通道，由于缺乏在神经发生早期的比较研究，因此情况尚不清楚。已经描述了转录因子在体外和体内调节突触蛋白的表达。他们目前没有解释这些基因在不同神经元群体中的共同调控。神经元限制性沉默因子NRSF / REST靶向大型基因集，但并非编码泛神经元，突触和离子通道蛋白的所有基因。 NRSF / REST功能丧失与消音器至激活器转换研究之间的差异使该因素的全部功能隐含了意义。连同microRNA，剪接调节子，染色质重塑剂和越来越多的转录调节子，该因子被嵌入反馈回路中，具有协调神经元分化的潜力。在神经元诱导过程中，这些回路对关键神经元功能基础蛋白质的协调表达的精确调节是一个主要的新兴课题。

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