大脑皮层
多小脑回
成纤维细胞生长因子
神经科学
生物
皮质激素生成
皮质(解剖学)
音猬因子
电穿孔
解剖
细胞生物学
信号转导
基因
胚胎干细胞
癫痫
遗传学
受体
出处
期刊:Journal of the Pharmaceutical Society of Japan
日期:2021-03-01
卷期号:141 (3): 349-357
标识
DOI:10.1248/yakushi.20-00198-3
摘要
Folds of the cerebral cortex, which are called gyri and sulci, are one of the most prominent features of the mammalian brain. However, the mechanisms underlying the development and malformation of cortical folds are largely unknown, mainly because they are difficult to investigate in mice, whose brain do not have cortical folds. To investigate the mechanisms underlying the development and malformation of cortical folds, we developed a genetic manipulation technique for the cerebral cortex of gyrencephalic carnivore ferrets. Genes-of-interest can be expressed in the ferret cortex rapidly and efficiently. We also demonstrated that genes-of-interest can be knocked out in the ferret cortex by combining in utero electroporation and the CRISPR/Cas9 system. Using our technique, we found that fibroblast growth factor (FGF) signaling and sonic hedgehog (Shh) signaling are crucial for cortical folding. In addition, we found that FGF signaling and Shh signaling preferentially increased outer radial glial cells and the thickness of upper layers of the cerebral cortex. Furthermore, over-activation of FGF signaling and Shh signaling resulted in polymicrogyria. Our findings provide in vivo data about the mechanisms of cortical folding in gyrencephalic mammals. Our technique for the ferret cerebral cortex should be useful for investigating the mechanisms underlying the development and diseases of the cerebral cortex that cannot be investigated using mice.
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