DISC1 Regulates the Proliferation and Migration of Mouse Neural Stem/Progenitor Cells through Pax5, Sox2, Dll1 and Neurog2.
DISC1 Regulates the Proliferation and Migration of Mouse Neural Stem/Progenitor Cells through Pax5, Sox2, Dll1 and Neurog2.
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DISC1 通过 Pax5、Sox2、Dll1 和 Neurog2 调节小鼠神经干/祖细胞的增殖和迁移
DOI：
10.3389/fncel.2017.00261
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发表时间：
2017
影响因子：
5.3
通讯作者：
Feng L
中科院分区：
文献类型：
--
作者：
Wu Q;Tang W;Luo Z;Li Y;Shu Y;Yue Z;Xiao B;Feng L
背景：精神分裂症中断1（DISC 1）调节神经发生，是主要精神疾病的遗传危险因素。然而，DISC 1功能障碍如何在分子水平上影响神经发生和细胞周期进展仍然是未知的。在此，我们研究了DISC 1在体外调节小鼠神经干/祖细胞（MNSPCs）增殖、迁移、细胞周期进程和凋亡中的作用。方法：从小鼠胎脑中分离培养MNSPCs。逆转录病毒载体或siRNA用于操纵DISC 1在MNSPCs中的表达。采用细胞增殖实验、transwell系统和流式细胞术分析MNSPCs的增殖、迁移、细胞周期进程和凋亡。神经发生特异性聚合酶链反应（PCR）阵列用于识别DISC 1下游基因，并通过转染表达质粒和siRNA进行功能分析。结果：DISC 1的缺失降低了MNSPCs的增殖和迁移，而DISC 1的增加导致了MNSPCs增殖和迁移的增加。同时，G 0/G1期细胞比例的增加伴随着DISC 1水平的降低，但没有观察到发生凋亡的MNSPCs数量的显著变化。配对盒基因5（Pax 5）、性别决定区Y盒2（Sox 2）、δ样蛋白1（Dll 1）和神经生成素2（Neurog 2）作为DISC 1下游的候选分子出现，拯救实验表明，增加或减少任一分子的表达调节DISC 1改变的MNSPCs的增殖和迁移。结论：在MNSPC的增殖和迁移过程中，Pax 5、Sox 2、Dll 1和Neurog 2介导了DISC 1的活性。
Background: Disrupted-in-schizophrenia 1 (DISC1) regulates neurogenesis and is a genetic risk factor for major psychiatric disorders. However, how DISC1 dysfunction affects neurogenesis and cell cycle progression at the molecular level is still unknown. Here, we investigated the role of DISC1 in regulating proliferation, migration, cell cycle progression and apoptosis in mouse neural stem/progenitor cells (MNSPCs) in vitro. Methods: MNSPCs were isolated and cultured from mouse fetal hippocampi. Retroviral vectors or siRNAs were used to manipulate DISC1 expression in MNSPCs. Proliferation, migration, cell cycle progression and apoptosis of altered MNSPCs were analyzed in cell proliferation assays (MTS), transwell system and flow cytometry. A neurogenesis specific polymerase chain reaction (PCR) array was used to identify genes downstream of DISC1, and functional analysis was performed through transfection of expression plasmids and siRNAs. Results: Loss of DISC1 reduced proliferation and migration of MNSPCs, while an increase in DISC1 led to increased proliferation and migration. Meanwhile, an increase in the proportion of cells in G0/G1 phase was concomitant with reduced levels of DISC1, but significant changes were not observed in the number MNSPCs undergoing apoptosis. Paired box gene 5 (Pax5), sex determining region Y-box 2 (Sox2), delta-like1 (Dll1) and Neurogenin2 (Neurog2) emerged as candidate molecules downstream of DISC1, and rescue experiments demonstrated that increased or decreased expression of either molecule regulated proliferation and migration in DISC1-altered MNSPCs. Conclusion: These results suggest that Pax5, Sox2, Dll1 and Neurog2 mediate DISC1 activity in MNSPC proliferation and migration.
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影响因子：
2.7
作者：
Bani-Yaghoub, Mahmud;Tremblay, Roger G.;Sikorska, Marianna
通讯作者：
Sikorska, Marianna
影响因子：
11
作者：
Camargo, L. M.;Collura, V.;Brandon, N. J.
通讯作者：
Brandon, N. J.
影响因子：
10.5
作者：
Blackwood, DHR;Visscher, PM;Muir, WJ
通讯作者：
Muir, WJ
DOI：
10.1016/j.bbrc.2008.10.120
发表时间：
2008-12-26
影响因子：
3.1
作者：
Bradshaw, Nicholas J.;Ogawa, Fumiaki;Millar, J. Kirsty
通讯作者：
Millar, J. Kirsty
影响因子：
56.9
作者：
BOTTARO, DP;RUBIN, JS;AARONSON, SA
通讯作者：
AARONSON, SA