MARVELD1 depletion leads to dysfunction of motor and cognition via regulating glia-dependent neuronal migration during brain development.
MARVELD1 depletion leads to dysfunction of motor and cognition via regulating glia-dependent neuronal migration during brain development.
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MARVELD1缺失通过调节大脑发育过程中神经胶质依赖性神经元迁移导致运动和认知功能障碍
DOI：
10.1038/s41419-018-1027-6
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发表时间：
2018-09-24
影响因子：
9
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Liu W;Han F;Qu S;Yao Y;Zhao J;Akhtar ML;Ci Y;Zhang H;Li H;Zhao Y;Yue L;Zhang Y;Wang C;Li Y
神经元功能连接的建立依赖于神经元的迁移和神经元在发育中的准确定位。异常的神经元迁移可引发神经元成熟缺陷和细胞凋亡。然而，大脑发育过程中神经元迁移障碍的许多遗传基础仍不清楚。在这项研究中，我们报道了marveld1缺陷小鼠在大脑发育过程中由于异常的神经元迁移而表现出运动和认知功能障碍。MARVELD1基因敲除（KO）小鼠的大脑皮层和小脑的层状组织被破坏，表明径向神经元迁移受损。此外，我们以小脑为模型探讨了径向神经元迁移过程，结果表明，神经元的适当迁移依赖于发育中的脑胶质细胞中MARVELD1的表达。MARVELD1以胶质依赖的方式抑制ITGB1和FAK Tyr397磷酸化的表达。抑制MARVELD1/ITGB1/FAK信号通路可逆转体外神经元迁移缺陷。我们的研究结果表明，MARVELD1通过介导胶质纤维的形成和ITGB1/FAK信号通路来调节神经元迁移。小鼠大脑发育过程中，MARVELD1的缺失导致运动和认知功能的异常。
The establishment of functional neuronal connectivity is dependent on the neuronal migration and the accurate positioning of neurons in the developing brain. Abnormal neuronal migration can trigger neuronal maturation defects and apoptosis. However, many genetic bases remain unclear in neuronal migration disorders during brain development. In this study, we reported that MARVELD1-defected mice displayed motor and cognitive dysfunction resulting from aberrant neuronal migration during brain development. The laminar organization of the cerebral cortex and cerebellum in MARVELD1 knockout (KO) mice is disrupted, indicating impaired radial neuronal migration. Furthermore, we used the cerebellum as a model to explore the radial neuronal migration processes, and the results demonstrated that the proper neuronal migration depended on MARVELD1 expression in glial cells of the developing brain. MARVELD1 suppressed the expression of ITGB1 and FAK Tyr397 phosphorylation in glia-dependent manner. The inhibition of the MARVELD1/ITGB1/FAK signalling pathway in MARVELD1 KO mice could reverse the defects in neuronal migration in vitro. Our findings revealed that MARVELD1 regulated neuronal migration by mediating the formation of glial fibres and ITGB1/FAK signalling pathway. The depletion of MARVELD1 during mouse brain development led to the abnormity of motor and cognition functions.
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影响因子：
16.6
作者：
Bocchi R;Egervari K;Carol-Perdiguer L;Viale B;Quairiaux C;De Roo M;Boitard M;Oskouie S;Salmon P;Kiss JZ
通讯作者：
Kiss JZ
SNF2H介导的染色质组织和组蛋白H1动力学控制小脑形态发生和神经成熟。
影响因子：
16.6
作者：
Alvarez-Saavedra, Matias;De Repentigny, Yves;Lagali, Pamela S.;Ram, Edupuganti V. S. Raghu;Yan, Keqin;Hashem, Emile;Ivanochko, Danton;Huh, Michael S.;Yang, Doo;Mears, Alan J.;Todd, Matthew A. M.;Corcoran, Chelsea P.;Bassett, Erin A.;Tokarew, Nicholas J. A.;Kokavec, Juraj;Majumder, Romit;Ioshikhes, Ilya;Wallace, Valerie A.;Kothary, Rashmi;Meshorer, Eran;Stopka, Tomas;Skoultchi, Arthur I.;Picketts, David J.
通讯作者：
Picketts, David J.
DOI：
10.1146/annurev-cellbio-101512-122400
发表时间：
2013
影响因子：
11.3
作者：
Evsyukova I;Plestant C;Anton ES
通讯作者：
Anton ES
影响因子：
4.7
作者：
Cho W;Hagemann TL;Johnson DA;Johnson JA;Messing A
通讯作者：
Messing A
影响因子：
2.7
作者：
Driver, Ashley M.;Shumrick, Christopher;Stottmann, Rolf W.
通讯作者：
Stottmann, Rolf W.