Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex
Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex
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DOI：
10.7554/elife.32332
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发表时间：
2018-03-21
期刊：
影响因子：
7.7
通讯作者：
Hiller, Michael
中科院分区：
文献类型：
--
作者：
Florio, Marta;Heide, Michael;Hiller, Michael
要了解灵长类动物（尤其是人类）进化过程中新皮层扩张的分子基础，需要鉴定在发育中的新皮层的神经干细胞和祖细胞中特别活跃的基因。在这里，我们已经使用现有的转录组数据集进行全面的筛选蛋白质编码基因优先表达的胎儿人新皮层的祖细胞。我们发现，15个人类特异性基因表现出这样的表达，其中许多进化出不同的神经祖细胞类型的表达谱和水平相比，他们的祖先旁系。对一个这样的基因NOTCH 2NL的功能研究证明了其在小鼠中促进基础祖细胞增殖的能力。另外35个具有祖细胞富集表达的人类基因显示仅在灵长类动物中具有直系同源物。我们的研究提供了一个基因资源，这些基因是有前途的候选人，在灵长类动物，特别是人类的进化过程中发挥特定的，新颖的，新皮质发育的作用。
Understanding the molecular basis that underlies the expansion of the neocortex during primate, and notably human, evolution requires the identification of genes that are particularly active in the neural stem and progenitor cells of the developing neocortex. Here, we have used existing transcriptome datasets to carry out a comprehensive screen for protein-coding genes preferentially expressed in progenitors of fetal human neocortex. We show that 15 human specific genes exhibit such expression, and many of them evolved distinct neural progenitor cell type expression profiles and levels compared to their ancestral paralogs. Functional studies on one such gene, NOTCH2NL, demonstrate its ability to promote basal progenitor proliferation in mice. An additional 35 human genes with progenitor-enriched expression are shown to have orthologs only in primates. Our study provides a resource of genes that are promising candidates to exert specific, and novel, roles in neocortical development during primate, and notably human, evolution.