兴奋性突触后电位
抑制性突触后电位
点突变
神经科学
突变
神经元
生物
遗传学
基因
作者
Ke Zhang,Yu Fang,Jian Zhu,Sue Han,Jiehui Chen,Xuanyuan Wu,Yingying Chen,Tingyu Shen,Jiaoyang Liao,Wenke Guo,Xianfa Yang,Ran Wang,Yun Qian,Jiaxin Yang,Leping Cheng,Yun Zhao,Chi‐chung Hui,Jinsong Li,Guangdun Peng,Shuijin He
出处
期刊:Cell Reports
[Cell Press]
日期:2020-04-01
卷期号:31 (3): 107521-107521
被引量:53
标识
DOI:10.1016/j.celrep.2020.03.085
摘要
Recent studies have revealed an essential role for embryonic cortical development in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, the genetic basis and underlying mechanisms remain unclear. Here, we generate mutant human embryonic stem cell lines (Mut hESCs) carrying an NR2F1-R112K mutation that has been identified in a patient with ASD features and investigate their neurodevelopmental alterations. Mut hESCs overproduce ventral telencephalic neuron progenitors (ventral NPCs) and underproduce dorsal NPCs, causing the imbalance of excitatory/inhibitory neurons. These alterations can be mainly attributed to the aberrantly activated Hedgehog signaling pathway. Moreover, the corresponding Nr2f1 point-mutant mice display a similar excitatory/inhibitory neuron imbalance and abnormal behaviors. Antagonizing the increased inhibitory synaptic transmission partially alleviates their behavioral deficits. Together, our results suggest that the NR2F1-dependent imbalance of excitatory/inhibitory neuron differentiation caused by the activated Hedgehog pathway is one precursor of neurodevelopmental disorders and may enlighten the therapeutic approaches.
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