Expression analyses of PLEKHG2, a Rho family-specific guanine nucleotide exchange factor, during mouse brain development
Expression analyses of PLEKHG2, a Rho family-specific guanine nucleotide exchange factor, during mouse brain development
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DOI：
10.1007/s00795-020-00275-1
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发表时间：
2021-01-25
影响因子：
1.8
通讯作者：
Nagata, Koh-ichi
中科院分区：
文献类型：
--
作者：
Nishikawa, Masashi;Ito, Hidenori;Nagata, Koh-ichi
编码Rho家族特异性鸟嘌呤核苷酸交换因子的PLEKHG 2基因缺失与小头畸形伴智力残疾有关。然而，不仅PLEKHG 2在发育过程中的作用，而且其表达谱也是未知的。在这项研究中，我们制备了一种针对PLEKHG 2的特异性抗体，并用小鼠组织进行了表达分析。在蛋白质印迹中，PLEKHG 2在成年小鼠中表现出组织依赖性的表达谱，并且在脑中以发育阶段依赖性的方式表达。然后，在免疫组织化学分析中，虽然PLEKHG 2在胚胎第14天在大脑皮层的皮质板和脑室区表面观察到，但在皮质发育期间，它分布在整个大脑皮层的II/III层和V层中。PLEKHG 2在P7时主要在海马CA区和齿状回的神经元核中表达。值得注意的是，核积累在P30消失，PLEKHG 2在这个时间点开始位于轴突和/或树突。此外，在体外免疫荧光显示，PLEKHG 2至少部分地定位在兴奋性和抑制性突触在原代培养的海马神经元。这些结果表明PLEKHG 2在中枢神经组织发育和突触功能中的作用。
Abnormalities of PLEKHG2 gene, encoding a Rho family-specific guanine nucleotide exchange factor, are involved in microcephaly with intellectual disability. However, not only the role of PLEKHG2 in the developmental process but also its expression profile is unknown. In this study, we prepared a specific antibody against PLEKHG2 and carried out expression analyses with mouse tissues. In western blotting, PLEKHG2 exhibited a tissue-dependent expression profile in adult mouse and was expressed in a developmental stage-dependent manner in brain. Then, in immunohistochemical analyses, while PLEKHG2 was observed in the cortical plate and ventricular zone surface of the cerebral cortex at embryonic day 14, it came to be distributed throughout the cerebral cortex in layer II/III and V during corticogenesis. PLEKHG2 was also detected mainly in the nucleus of neurons in the hippocampal CA regions and dentate gyrus at P7. Notably, the nuclear accumulation disappeared at P30 and PLEKHG2 came to be located at the axons and/or dendrites at this time point. Moreover, in vitro immunofluorescence revealed that PLEKHG2 was at least partially localized at both excitatory and inhibitory synapses in primary cultured hippocampal neurons. These results suggest roles of PLEKHG2 in the development of the central nervous tissue and synaptic function.