Experience-dependent transcriptional regulation in juvenile brain development
Experience-dependent transcriptional regulation in juvenile brain development
复制标题
青少年大脑发育中的经验依赖性转录调控
DOI：
10.1111/dgd.12571
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Sugiyama Sayaka
中科院分区：
文献类型：
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作者：
Sakai Akiko;Sugiyama Sayaka
在大脑发育过程中，一旦初级神经网络形成，它们在很大程度上受到环境刺激的影响。青少年的大脑有一个独特的时间窗口，称为关键期，在此期间，神经回路被经验重塑。越来越多的证据表明，生命早期异常的电路重新布线会导致生命后期的各种神经发育障碍。最近的研究暗示了关键时期激活的两个重要方面，这两个方面都是经验依赖的：(a)在抑制性中间神经元的发育轨迹中实现神经回路的适当兴奋/抑制（E/I）平衡；(b)表观遗传调控允许神经元可塑性的灵活基因表达。本文从转录调控和染色质调控的角度探讨了青少年大脑可塑性的分子机制，重点讨论了Otx2同型蛋白。根据经验，Otx2被转运到皮质小白蛋白阳性的中间神经元（PV细胞），在那里它诱导PV细胞成熟以激活关键时期。因此，了解Otx2作为经验“信使”的独特行为和功能，将有助于深入了解青少年大脑发育的机制。最近发现的Otx2的下游靶点表明，Otx2在PV细胞的稳态中起着新的作用，而且在染色质状态的调节中起着重要的作用，这对神经元的可塑性很重要。我们进一步讨论了在出生后大脑发育跨越关键时期的表观遗传变化。染色质调控的不同方面可能是经验依赖性神经元发育和可塑性的基础。
During brain development, once primary neural networks are formed, they are largely sculpted by environmental stimuli. The juvenile brain has a unique time window termed the critical period, in which neuronal circuits are remodeled by experience. Accumulating evidence indicates that abnormal rewiring of circuits in early life contributes to various neurodevelopmental disorders at later stages of life. Recent studies implicate two important aspects for activation of the critical period, both of which are experience‐dependent: (a) proper excitatory/inhibitory (E/I) balance of neural circuit achieved during developmental trajectory of inhibitory interneurons, and (b) epigenetic regulation allowing flexible gene expression for neuronal plasticity. In this review, we discuss the molecular mechanisms of juvenile brain plasticity from the viewpoints of transcriptional and chromatin regulation, with a focus on Otx2 homeoprotein. Depending on experience, Otx2 is transported into cortical parvalbumin‐positive interneurons (PV cells), where it induces PV cell maturation to activate the critical period. Understanding the unique behavior and function of Otx2 as a “messenger” of experience should therefore provide insights into mechanisms of juvenile brain development. Recently identified downstream targets of Otx2 suggest novel roles of Otx2 in homeostasis of PV cells, and, moreover, in regulation of chromatin state, which is important for neuronal plasticity. We further discuss epigenetic changes during postnatal brain development spanning the critical period. Different aspects of chromatin regulation may underlie experience‐dependent neuronal development and plasticity.