The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice
复制标题
类人猿特异性基因 TBC1D3 促进小鼠基底神经祖细胞的产生并诱导皮质折叠。
DOI：
10.7554/elife.18197
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发表时间：
2016-08-09
期刊：
影响因子：
7.7
通讯作者：
Luo, Zhen-Ge
中科院分区：
文献类型：
--
作者：
Ju, Xiang-Chun;Hou, Qiong-Qiong;Luo, Zhen-Ge
皮层的扩张和折叠通常与高智商的进化有关，但皮层折叠背后的分子和细胞机制仍然知之甚少。类人猿特异性基因TBC1D3在类人猿进化过程中经历了片段复制，但其在大脑发育中的作用尚未被探索。本研究发现，TBC1D3在小鼠脑室皮层祖细胞中通过子宫内电穿孔表达，导致脑室径向胶质细胞（vRGs）分层，促进具有典型外径向胶质细胞（oRG）形态的自我更新基底祖细胞的产生，这种细胞在灵长类动物中最为丰富。此外，在培养的人脑切片中，下调TBC1D3可减少oRGs的产生。有趣的是，由子宫内电穿孔或TBC1D3转基因表达引起的局部oRG增殖经常被发现是皮层区域折叠的基础。因此，我们已经确定了一个类人猿基因，该基因在调节皮质扩张和折叠中需要oRG的产生。
Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding.