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草莓缺口同源物1在皮质神经元轴突生长中的作用。

Involvement of strawberry notch homologue 1 in neurite outgrowth of cortical neurons.

作者信息

Erkhembaatar Munkhsoyol, Yamamoto Iroha, Inoguchi Fuduki, Taki Kosuke, Yamagishi Satoru, Delaney Leanne, Mariko Nishibe, Abe Takaya, Kiyonari Hiroshi, Hanashima Carina, Naka-Kaneda Hayato, Ihara Dai, Katsuyama Yu

机构信息

Division of Neuroanatomy, Department of Anatomy, Shiga University of Medical Science, Otsu, Japan.

Department of Anatomy & Neuroscience, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

Dev Growth Differ. 2022 Sep;64(7):379-394. doi: 10.1111/dgd.12802. Epub 2022 Sep 3.

Abstract

When the regulation of axonal and dendritic growth is altered, the neuronal network becomes disordered, which may contribute to the development of psychiatric disorders. Some genome analyses have suggested relationships between mutations in strawberry notch homologue 1 (SBNO1) and neurodevelopmental disorders. However, the function of SBNO1 has not yet been reported. Here, SBNO1 expression pattern during the development of the cerebral cortex in mice was examined. SBNO1 was strongly expressed in the cortical plate and its expression was maintained at a low level during the postnatal stage. CRISPR/Cas9-based knockout of Sbno1 in Neuro2A cultured cells showed delayed growth of neurites. A cortical neuron-specific conditional knockout mouse was constructed, which resulted in hypotrophy of axon bundles and dendrites in cortical neurons. Thus, when mutated, SBNO1 is a candidate gene for psychiatric diseases, such as schizophrenia, as suggested by human genome studies.

摘要

当轴突和树突生长的调节发生改变时,神经网络会变得紊乱,这可能有助于精神疾病的发展。一些基因组分析表明草莓缺口同源物1(SBNO1)突变与神经发育障碍之间存在关联。然而,SBNO1的功能尚未见报道。在此,研究了小鼠大脑皮质发育过程中SBNO1的表达模式。SBNO1在皮质板中强烈表达,且在出生后阶段其表达维持在低水平。在Neuro2A培养细胞中基于CRISPR/Cas9的Sbno1基因敲除显示神经突生长延迟。构建了皮质神经元特异性条件性敲除小鼠,结果导致皮质神经元轴突束和树突萎缩。因此,如人类基因组研究所示,当发生突变时,SBNO1是精神疾病如精神分裂症的候选基因。

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