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皮层发育中的翻译调控。

Translational control in cortical development.

作者信息

Cremisi Federico, Vignali Robert

机构信息

Laboratory of Biology, Department of Sciences, Scuola Normale Superiore, Pisa, Italy.

Department of Biology, University of Pisa, Pisa, Italy.

出版信息

Front Neuroanat. 2023 Jan 9;16:1087949. doi: 10.3389/fnana.2022.1087949. eCollection 2022.

Abstract

Differentiation of specific neuronal types in the nervous system is worked out through a complex series of gene regulation events. Within the mammalian neocortex, the appropriate expression of key transcription factors allocates neurons to different cortical layers according to an inside-out model and endows them with specific properties. Precise timing is required to ensure the proper sequential appearance of key transcription factors that dictate the identity of neurons within the different cortical layers. Recent evidence suggests that aspects of this time-controlled regulation of gene products rely on post-transcriptional control, and point at micro-RNAs (miRs) and RNA-binding proteins as important players in cortical development. Being able to simultaneously target many different mRNAs, these players may be involved in controlling the global expression of gene products in progenitors and post-mitotic cells, in a gene expression framework where parallel to transcriptional gene regulation, a further level of control is provided to refine and coordinate the appearance of the final protein products. miRs and RNA-binding proteins (RBPs), by delaying protein appearance, may play heterochronic effects that have recently been shown to be relevant for the full differentiation of cortical neurons and for their projection abilities. Such heterochronies may be the base for evolutionary novelties that have enriched the spectrum of cortical cell types within the mammalian clade.

摘要

神经系统中特定神经元类型的分化是通过一系列复杂的基因调控事件实现的。在哺乳动物新皮层中,关键转录因子的适当表达根据由内向外的模型将神经元分配到不同的皮层层,并赋予它们特定的特性。需要精确的时间安排来确保关键转录因子按顺序适时出现,这些转录因子决定了不同皮层层内神经元的特性。最近的证据表明,这种对基因产物的时间控制调节在一定程度上依赖于转录后调控,并指出微小RNA(miRs)和RNA结合蛋白在皮层发育中起着重要作用。由于能够同时靶向许多不同的mRNA,这些分子可能参与控制祖细胞和有丝分裂后细胞中基因产物的整体表达,在一个与转录基因调控并行的基因表达框架中,提供了进一步的调控水平,以优化和协调最终蛋白质产物的出现。miRs和RNA结合蛋白(RBPs)通过延迟蛋白质的出现,可能发挥异时性效应,最近的研究表明,这种效应与皮层神经元的完全分化及其投射能力有关。这种异时性可能是进化新特征的基础,这些新特征丰富了哺乳动物类群中皮层细胞类型的谱系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdb8/9868627/74904ab8c714/fnana-16-1087949-g0001.jpg

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