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Comparative gene expression analysis of the engulfment and cell motility (ELMO) protein family in the mouse brain.
Gene Expression Patterns ( IF 1.2 ) Pub Date : 2019-09-12 , DOI: 10.1016/j.gep.2019.119070
Yumi Sato 1 , Akira Sato 2 , Shota Mizuno 3 , Jun-Na Hirota 3 , Shuhei Fujima 3 , Chiaki Ishii 3 , Yoshitake Sano 3 , Teiichi Furuichi 2
Affiliation  

Engulfment and cell motility (ELMO) proteins bind to Dock180, a guanine nucleotide exchange factor (GEF) of the Rac family, and regulate GEF activity. The resultant ELMO/Dock180/Rac module regulates cytoskeletal reorganization responsible for the engulfment of apoptotic cells, cell migration, and neurite extension. The expression and function of Elmo family proteins in the nervous system, however, are not yet fully understood. Here, we characterize the comparative gene expression profiles of three Elmo family members (Elmo1, Elmo2, and Elmo3) in the brain of C57BL/6J mice, a widely used inbred strain, together with reeler mutant mice to understand gene expression in normal laminated brain areas compared with abnormal areas. Although all three Elmo genes showed widespread mRNA expression over various mouse tissues tested, Elmo1 and Elmo2 were the major types expressed in the brain, and three Elmo genes were up-regulated between the first postnatal week (infant stage) and the third postnatal week (juvenile, weaning stage). In addition, the mRNAs of Elmo genes showed distinct distribution patterns in various brain areas and cell-types; such as neurons including inhibitory interneurons as well as some non-neuronal cells. In the cerebral cortex, the three Elmo genes were widely expressed over many cortical regions, but the predominant areas of Elmo1 and Elmo2 expression tended to be distributed unevenly in the deep (a lower part of the VI) and superficial (II/III) layers, respectively, which also changed depending on the cortical areas and postnatal stages. In the dentate gyrus of the hippocampus, Elmo2 was expressed in dentate granule cells more in the mature stage rather than the immature-differentiating stage. In the thalamus, Elmo1 but not the other members was highly expressed in many nuclei. In the medial habenula, Elmo2 and Elmo3 were expressed at intermediate levels. In the cerebellar cortex, Elmo1 and Elmo2 were expressed in differentiating-mature granule cells and mature granule cells, respectively. In the Purkinje cell layer, Elmo1 and Elmo2 were expressed in Purkinje cells and Bergmann glia, respectively. Disturbed cellular distributions and laminar structures caused by the reeler mutation did not severely change expression in these cell types despite the disturbed cellular distributions and laminar structures, including those of the cerebrum, hippocampus, and cerebellum. Taken together, these results suggested that these three Elmo family members share their functional roles in various brain regions during prenatal-postnatal development.



中文翻译:

小鼠脑中吞噬和细胞运动(ELMO)蛋白家族的比较基因表达分析。

吞噬和细胞运动(ELMO)蛋白与Rac家族的鸟嘌呤核苷酸交换因子(GEF)Dock180结合,并调节GEF活性。最终的ELMO / Dock180 / Rac模块调节负责凋亡细胞吞噬,细胞迁移和神经突扩展的细胞骨架重组。然而,尚未完全了解Elmo家族蛋白在神经系统中的表达和功能。在这里,我们表征了广泛使用的自交系C57BL / 6J小鼠的大脑中三个Elmo家族成员(Elmo1Elmo2Elmo3)的比较基因表达谱,以及相关的绕线突变小鼠了解正常叠层脑区与异常区相比的基因表达。尽管所有三个Elmo基因均在测试的各种小鼠组织中均显示了广泛的mRNA表达,但Elmo1Elmo2是大脑中表达的主要类型,并且三个Elmo基因在出生后第一周(婴儿阶段)至出生后第三周之间上调(少年,断奶阶段)。此外,Elmo基因的mRNA在不同的大脑区域和细胞类型中表现出明显的分布模式。例如包括抑制性中间神经元在内的神经元以及一些非神经元细胞。在大脑皮层中,三只Elmo基因在许多皮层区域广泛表达,但是Elmo1Elmo2的主要表达区域倾向于分别在深层(VI的下部)和浅层(II / III)中分布不均匀,并且根据皮质区域和产后阶段。在海马的齿状回中,Elmo2在齿状颗粒细胞中的表达更多于成熟阶段,而不是未成熟分化阶段。在丘脑中,Elmo1在其他原子核中高度表达,但其他成员则没有。在内侧ha中,Elmo2Elmo3以中等水平表达。在小脑皮质中,Elmo1Elmo2分别在分化成熟的颗粒细胞和成熟的颗粒细胞中表达。在Purkinje细胞层中,Elmo1Elmo2分别在Purkinje细胞和Bergmann胶质细胞中表达。尽管受到干扰的细胞分布和层状结构(包括大脑,海马和小脑的分布)受到干扰,但由reeler突变引起的扰乱的细胞分布和层状结构并未严重改变这些细胞类型的表达。综上,这些结果表明,这三个Elmo家族成员在产前-产后发育过程中在各个大脑区域中共享其功能性角色。

更新日期:2019-09-12
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