A discrete subtype of neural progenitor crucial for cortical folding in the gyrencephalic mammalian brain

A discrete subtype of neural progenitor crucial for cortical folding in the gyrencephalic mammalian brain
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DOI:
10.7554/elife.54873
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发表时间:
2020-04-21
期刊:
影响因子:
7.7
通讯作者:
Kawasaki, Hiroshi
Kawasaki, Hiroshi
中科院分区:
生物学1区
文献类型:
--
作者:
Matsumoto, Naoyuki;Tanaka, Satoshi;Kawasaki, Hiroshi

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神经祖细胞亚型多样性的增加和大脑皮层的折叠是哺乳动物大脑进化过程中出现的特征。在这里,我们表明,一个特定亚型的神经祖细胞的扩张是至关重要的皮质折叠。我们发现外放射状胶质细胞(oRG)可以通过HOPX在雪貂脑回皮质的表达进行细分。与hopx阴性的oRG细胞相比,hopx阳性的oRG细胞具有较高的自我更新活性,并积聚在前瞻性的脑回区。利用我们对雪貂的体内遗传操作技术,我们发现hopx阳性oRG细胞的数量及其自我更新活性受到sonic hedgehog (Shh)信号的调节。重要的是,抑制Shh信号减少了hopx阳性的oRG细胞和皮质折叠,而增强它具有相反的作用。我们的研究结果揭示了一种新的神经祖细胞亚型,对脑回型哺乳动物大脑皮层的皮层折叠很重要。
An increase in the diversity of neural progenitor subtypes and folding of the cerebral cortex are characteristic features which appeared during the evolution of the mammalian brain. Here, we show that the expansion of a specific subtype of neural progenitor is crucial for cortical folding. We found that outer radial glial (oRG) cells can be subdivided by HOPX expression in the gyrencephalic cerebral cortex of ferrets. Compared with HOPX-negative oRG cells, HOPX-positive oRG cells had high self-renewal activity and were accumulated in prospective gyral regions. Using our in vivo genetic manipulation technique for ferrets, we found that the number of HOPX-positive oRG cells and their self-renewal activity were regulated by sonic hedgehog (Shh) signaling. Importantly, suppressing Shh signaling reduced HOPX-positive oRG cells and cortical folding, while enhancing it had opposing effects. Our results reveal a novel subtype of neural progenitor important for cortical folding in gyrencephalic mammalian cerebral cortex.