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Convergent microRNA actions coordinate neocortical development

机译:聚合的microRNA作用协调新皮层的发育

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摘要

Neocortical development is a complex process that, at the cellular level, involves tight control of self-renewal, cell fate commitment, survival, differentiation and delamination/migration. These processes require, at the molecular level, the precise regulation of intrinsic signaling pathways and extrinsic factors with coordinated action in a spatially and temporally specific manner. Transcriptional regulation plays an important role during corticogenesis; however, microRNAs (miRNAs) are emerging as important post-transcriptional regulators of various aspects of central nervous system development. miRNAs are a class of small, single-stranded noncoding RNA molecules that control the expression of the majority of protein coding genes (i.e., targets). How do different miRNAs achieve precise control of gene networks during neocortical development? Here, we critically review all the miRNA–target interactions validated in vivo, with relevance to the generation and migration of pyramidal-projection glutamatergic neurons, and for the initial formation of cortical layers in the embryonic development of rodent neocortex. In particular, we focus on convergent miRNA actions, which are still a poorly understood layer of complexity in miRNA signaling, but potentially one of the keys to disclosing how miRNAs achieve the precise coordination of complex biological processes such as neocortical development.
机译:新皮层发育是一个复杂的过程,在细胞水平上涉及对自我更新,细胞命运的承诺,存活,分化和分层/迁移的严格控制。这些过程需要在分子水平上对内在信号传导途径和外在因素进行精确调控,并以空间和时间上特定的方式发挥协调作用。转录调节在皮质发生过程中起重要作用。然而,microRNA(miRNA)逐渐成为中枢神经系统发育各个方面的重要转录后调节因子。 miRNA是一类小的单链非编码RNA分子,可控制大多数蛋白质编码基因(即靶标)的表达。在新皮层发育过程中,不同的miRNA如何实现对基因网络的精确控制?在这里,我们严格审查所有在体内验证的miRNA-靶标相互作用,与锥体投射谷氨酸能神经元的产生和迁移有关,以及在啮齿动物新皮层的胚胎发育中皮质层的初始形成。特别是,我们专注于收敛的miRNA作用,这仍然是人们对miRNA信号复杂性了解甚少的一层,但可能是揭示miRNA如何实现复杂的生物学过程(如新皮层发育)的精确协调的关键之一。

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