An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals.
An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals.
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DOI：
10.1038/srep29578
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发表时间：
2016-07-12
影响因子：
4.6
通讯作者：
Kawasaki H
中科院分区：
文献类型：
--
作者：
Toda T;Shinmyo Y;Dinh Duong TA;Masuda K;Kawasaki H
由于哺乳动物大脑中大脑皮层的折叠被认为对于高级大脑功能至关重要，因此其在发育和进化过程中形成的机制引起了人们的极大兴趣。尽管有人提出脑室下区（SVZ）中增加的神经祖细胞负责形成皮质褶皱，但它们在皮质褶皱中的作用仍然很大程度上不清楚，这主要是因为环脑哺乳动物的遗传方法很少可用。在这里，通过利用我们新开发的针对雪貂环脑的子宫内电穿孔技术，我们研究了 SVZ 祖细胞在皮质折叠中的作用。我们发现，即使在皮质褶皱开始形成之前，发育中的雪貂大脑中 SVZ 祖细胞的丰度也存在区域差异。当Tbr2转录因子被抑制时，雪貂大脑皮层中的中间祖细胞显着减少。有趣的是，抑制 Tbr2 也可以减少外放射状胶质细胞的数量。我们发现 SVZ 祖细胞数量减少会导致皮质折叠受损。当 Tbr2 被抑制时，与脑沟相比，脑回的上皮层优先减少。我们的研究结果表明 SVZ 祖细胞在环脑皮质折叠中的生物学重要性。
Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain.