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Growth arrest specific gene 7 is associated with schizophrenia and regulates neuronal migration and morphogenesis
Zhengrong Zhang1; Fanfan Zheng2; Yang You1; Yuanlin Ma1; Weihua Yue1; Dai Zhang1
2016
发表期刊Molecular Brain
期号9页码:54
摘要

BACKGROUND:

Schizophrenia is a highly heritable chronic mental disorder with significant abnormalities in brain function. The neurodevelopmental hypothesis proposes that schizophrenia originates in the prenatal period due to impairments in neuronal developmental processes such as migration and arborization, leading to abnormal brain maturation. Previous studies have identified multiple promising candidate genes that drive functions in neurodevelopment and are associated with schizophrenia. However, the molecular mechanisms of how they exert effects on the pathophysiology of schizophrenia remain largely unknown.

RESULTS:

In our research, we identified growth arrest specific gene 7 (GAS7) as a schizophrenia risk gene in two independent Han Chinese populations using a two-stage association study. Functional experiments were done to further explore the underlying mechanisms of the role of Gas7 in cortical development. In vitro, we discovered that Gas7 contributed to neurite outgrowth through the F-BAR domain. In vivo, overexpression of Gas7 arrested neuronal migration by increasing leading process branching, while suppression of Gas7 could inhibit neuronal migration by lengthening leading processes. Through a series of behavioral tests, we also found that Gas7-deficient mice showed sensorimotor gating deficits.

CONCLUSIONS:

Our results demonstrate GAS7 as a susceptibility gene for schizophreniaGas7 might participate in the pathogenesis of schizophrenia by regulating neurite outgrowth and neuronal migration through its C-terminal F-BAR domain. The impaired pre-pulse inhibition (PPI) of Gas7-deficient mice might mirror the disease-related behavior in schizophrenia.

其他摘要英文摘要
关键词Gas7 Neurite Outgrowth Neuronal Migration Schizophrenia
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/12120
专题脑网络组研究中心
通讯作者Fanfan Zheng
作者单位1.Institute of Mental Health, The Sixth Hospital, Peking University
2.Brainnetome Center, Institute of Automation, Chinese Academy of Sciences
推荐引用方式
GB/T 7714
Zhengrong Zhang,Fanfan Zheng,Yang You,et al. Growth arrest specific gene 7 is associated with schizophrenia and regulates neuronal migration and morphogenesis[J]. Molecular Brain,2016(9):54.
APA Zhengrong Zhang,Fanfan Zheng,Yang You,Yuanlin Ma,Weihua Yue,&Dai Zhang.(2016).Growth arrest specific gene 7 is associated with schizophrenia and regulates neuronal migration and morphogenesis.Molecular Brain(9),54.
MLA Zhengrong Zhang,et al."Growth arrest specific gene 7 is associated with schizophrenia and regulates neuronal migration and morphogenesis".Molecular Brain .9(2016):54.
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