对皮质脊髓系统发育和演变的控制
Sungbo Shim1, Kenneth Y Kwan, Mingfeng Li
1Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nature
|June 9, 2012
概括
研究人员发现了一种控制皮质脊髓神经元发育的基因调节元件. 这个元素,E4,与SOX转录因子相互作用,以确保哺乳动物的正确脑电线和皮质层形成.
科学领域:
- 神经科学是一个神经科学.
- 发育生物学 发展生物学
- 进化生物学 进化生物学
背景情况:
- 哺乳动物的六层大脑新皮质和皮质脊髓管是关键的进化创新.
- 控制新皮层发育和进化的遗传机制尚未完全理解.
研究的目的:
- 确定调节皮质脊髓神经元发育的遗传元素.
- 阐明哺乳动物新皮质调节网络的进化起源.
主要方法:
- 鉴定了一种保存的非外来元素 (E4),作为Fezf2基因的皮质特异增强剂.
- 分析SOX4,SOX11和SOX5与E4元素的相互作用.
- 在皮质中通过CRISPR中介删除Sox4和Sox11,以评估对Fezf2表达和神经元发育的影响.
- 在四足动物进化过程中对E4中的SOX结合部位进行比较分析.
主要成果:
- E4作为Fezf2的关键增强剂,Fezf2是一种对皮质脊髓神经元认同至关重要的基因.
- SOX4和SOX11激活E4,与抑制器SOX5.5进行竞争.
- 删除Sox4和Sox11会破坏Fezf2的表达,损害皮质脊髓神经元的特异性,并导致类似卷轴器的皮质层层缺陷.
- 证据表明,在四足动物和哺乳动物进化过程中,E4中功能性SOX结合部位的进化.
结论:
- SOX转录因子聚集在Fezf2增强剂E4上,以调节皮质脊髓神经元发育.
- 这种调节网络对于建立神经元身份,连接性和皮质架构至关重要.
- 这些发现为哺乳动物新皮层进化的遗传基础提供了洞察力.
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