Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion
Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion
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DOI：
10.1126/science.aaa1975
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发表时间：
2015-03-27
期刊：
影响因子：
56.9
通讯作者：
Huttner, Wieland B.
中科院分区：
文献类型：
--
作者：
Florio, Marta;Albert, Mareike;Huttner, Wieland B.
人类新皮质的进化扩张反映了脑室下区基础祖细胞的放大，在胎儿皮质生成过程中产生了更多的神经元。在这项工作中，我们分析了不同的祖细胞亚群的转录，这些亚群是通过基于细胞极性的方法从发育中的小鼠和人类新皮质中分离出来的。我们鉴定了56个基因，这些基因在人的顶端和基底部的放射状胶质细胞中优先表达，缺乏小鼠的同源基因。其中，ARHGAP11B具有最高程度的放射状胶质细胞特异性表达。ARHGAP11B是从黑猩猩谱系分离后，在人类谱系上部分复制ARHGAP11A(编码Rho鸟苷三磷酸酶激活蛋白)而产生的。ARHGAP11B在胚胎小鼠新皮质中的表达可促进基础祖细胞的生成和自我更新，并可增加皮质板面积和诱导脑回旋。因此，ARHGAP11B可能参与了人类大脑皮层的进化扩张。
Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. In this work, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.