Genomic divergence and brain evolution: How regulatory DNA influences development of the cerebral cortex.
Genomic divergence and brain evolution: How regulatory DNA influences development of the cerebral cortex.
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DOI：
10.1002/bies.201500108
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发表时间：
2016-02
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影响因子：
--
通讯作者：
Silver DL
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文献类型：
--
作者：
Silver DL
大脑皮层控制着我们最独特的高级认知功能。人类特有的基因表达差异在大脑皮层中非常丰富，但我们才刚刚开始了解这些差异如何影响大脑功能。这篇综述讨论了当前将非编码调控 DNA 变化（包括增强子）与新皮质进化联系起来的证据。使用动物模型进行的功能研究揭示了我们的基因组在皮质发育的关键方面（包括祖细胞周期和神经元信号传导）中的聚合作用。包括 iPS 细胞和类器官在内的新技术为在相关物种环境中模拟进化修饰提供了潜在的替代方案。与其他灵长类动物相比，几种根植于大脑皮层的疾病在人类身上表现得独一无二，因此凸显了了解人类大脑差异的重要性。未来对调控位点（包括与疾病有关的调控位点）的研究将共同帮助阐明我们独特的认知特征背后的关键细胞和遗传机制。
The cerebral cortex controls our most distinguishing higher cognitive functions. Human-specific gene expression differences are abundant in the cerebral cortex, yet we have only begun to understand how these variations impact brain function. This review discusses the current evidence linking non-coding regulatory DNA changes, including enhancers, with neocortical evolution. Functional interrogation using animal models reveals converging roles for our genome in key aspects of cortical development including progenitor cell cycle and neuronal signaling. New technologies, including iPS cells and organoids, offer potential alternatives to modeling evolutionary modifications in a relevant species context. Several diseases rooted in the cerebral cortex uniquely manifest in humans compared to other primates, thus highlighting the importance of understanding human brain differences. Future studies of regulatory loci, including those implicated in disease, will collectively help elucidate key cellular and genetic mechanisms underlying our distinguishing cognitive traits.