Department of Signal Transduction, Research Institute for Microbial Disease, Osaka University, 3-1 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Department of Signal Transduction, Research Institute for Microbial Disease, Osaka University, 3-1 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Neurochem Int. 2019 Oct;129:104465. doi: 10.1016/j.neuint.2019.104465. Epub 2019 May 13.
The GINS (Go, Ichi, Nii, and San) complex contains four protein subunits (PSF1, PSF2, PSF3, and SLD5) and has been identified as a factor essential for the initiation and elongation stages of the DNA replication process. A previous study indicated that PSF2 participated in the developing central nervous system (CNS) of Xenopus laevis. However, the expression and function of GINS members in the mammalian developing nervous system remains unclear. Here, we examined the expression of GINS members in mice during nervous system development via immunofluorescence staining. At the beginning of neural development, PSF1 and SLD5 were highly expressed in neuroepithelial stem cells (NSCs) of the inner surface of neural tube (NT) and overlapped with proliferation marker Ki67. After entering the mid- and late-phase of neural development, PSF1 and SLD5 changed their regions of expression. These genes were highly expressed in dorsal root ganglion (DRG) progenitors, but they showed no overlap with Ki67 positive cells. Instead, a reduction of SLD5 expression promoted neuronal differentiation and maturation in the late-phase. PSF2 and PSF3 showed no tissue-specificity. PSF2 was constitutively and highly expressed whereas PSF3 was expressed at very low levels during neural development. In this study, we demonstrated variations in proteins and expression regions of the GINS members during mammalian CNS development and revealed a correlation between GINS expression and cell proliferation. Furthermore, we have suggested a novel function of GINS member SLD5, which regulates the differentiation of neural stem/progenitors.
GINS（Go、Ichi、Nii 和 San）复合物包含四个蛋白质亚基（PSF1、PSF2、PSF3 和 SLD5），已被鉴定为 DNA 复制过程起始和延伸阶段所必需的因子。先前的研究表明 PSF2 参与了非洲爪蟾的发育中的中枢神经系统（CNS）。然而，GINS 成员在哺乳动物发育中的神经系统中的表达和功能仍不清楚。在这里，我们通过免疫荧光染色检查了 GINS 成员在小鼠神经系统发育过程中的表达。在神经发育的早期，PSF1 和 SLD5 在神经管（NT）内表面的神经上皮干细胞（NSC）中高度表达，并与增殖标志物 Ki67 重叠。进入神经发育的中期和晚期后，PSF1 和 SLD5 改变了它们的表达区域。这些基因在背根神经节（DRG）祖细胞中高度表达，但与 Ki67 阳性细胞无重叠。相反，SLD5 表达的减少促进了晚期神经元的分化和成熟。PSF2 和 PSF3 没有组织特异性。PSF2 持续且高度表达，而 PSF3 在神经发育过程中表达水平极低。在这项研究中，我们展示了 GINS 成员在哺乳动物 CNS 发育过程中的蛋白质和表达区域的变化，并揭示了 GINS 表达与细胞增殖之间的相关性。此外，我们提出了 GINS 成员 SLD5 的新功能，它调节神经干细胞/祖细胞的分化。
