The Primate-Specific Gene TMEM14B Marks Outer Radial Glia Cells and Promotes Cortical Expansion and Folding
The Primate-Specific Gene TMEM14B Marks Outer Radial Glia Cells and Promotes Cortical Expansion and Folding
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灵长类动物特异性基因 TMEM14B 标记外放射状胶质细胞并促进皮质扩张和折叠
DOI：
10.1016/j.stem.2017.08.013
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发表时间：
2017-11-02
期刊：
影响因子：
23.9
通讯作者：
Wang, Xiaoqun
中科院分区：
文献类型：
--
作者：
Liu, Jing;Liu, Wensu;Wang, Xiaoqun
人类大脑的进化与新皮层的扩张和折叠有关。神经祖细胞（NP）群体（如位于基底部的放射状胶质细胞[RG]，位于扩大的外室下区[OSVZ]）的多样性增加可能有助于这种进化扩张，尽管它们的特征和相对贡献仅部分了解。通过分选的人NP亚群的单细胞转录谱分析，我们鉴定了灵长类特异性TMEM 14 B基因作为基础RG的标记。TMEM 14 B在胚胎NPs中的表达诱导出生后小鼠的皮质增厚和脑回化。这伴随着SVZ扩张，外部RG样细胞的出现，以及多个NP亚群的增殖，所有皮质层和正常层压成比例增加。TMEM 14 B通过增加IQGAP 1的磷酸化和核转位来驱动NP增殖，这反过来促进G1/S细胞周期转换。这些数据表明，单个灵长类特异性基因可以驱动神经发育变化，从而促进大脑进化。
Human brain evolution is associated with expansion and folding of the neocortex. Increased diversity in neural progenitor (NP) populations (such as basally located radial glia [RG], which reside in an enlarged outer subventricular zone [OSVZ]) likely contributes to this evolutionary expansion, although their characteristics and relative contributions are only partially understood. Through single-cell transcriptional profiling of sorted human NP subpopulations, we identified the primate-specific TMEM14B gene as a marker of basal RG. Expression of TMEM14B in embryonic NPs induces cortical thickening and gyrification in postnatal mice. This is accompanied by SVZ expansion, the appearance of outer RG-like cells, and the proliferation of multiple NP subsets, with proportional increases in all cortical layers and normal lamination. TMEM14B drives NP proliferation by increasing the phosphorylation and nuclear translocation of IQGAP1, which in turn promotes G1/S cell cycle transitions. These data show that a single primate-specific gene can drive neurodevelopmental changes that contribute to brain evolution.