Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression

Hasenpusch-Theil Kerstin; West Stephen; Kelman Alexandra; Kozic Zrinko; Horrocks Sophie; McMahon Andrew P.; Price David J.; Mason Jason O.; Theil Thomas

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Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression

机译：通过CDK6表达调节径向胶质细胞周期，GLI3通过CDK6表达来控制皮质神经发生的开始

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The cerebral cortex contains an enormous number of neurons, allowing it to perform highly complex neural tasks. Understanding how these neurons develop at the correct time and place and in accurate numbers constitutes a major challenge. Here, we demonstrate a novel role for Gli3, a key regulator of cortical development, in cortical neurogenesis. We show that the onset of neuron formation is delayed in Gli3 conditional mouse mutants. Gene expression profiling and cell cycle measurements indicate that shortening of the G1 and S phases in radial glial cells precedes this delay. Reduced G1 length correlates with an upregulation of the cyclin-dependent kinase gene Cdk6, which is directly regulated by Gli3. Moreover, pharmacological interference with Cdk6 function rescues the delayed neurogenesis in Gli3 mutant embryos. Overall, our data indicate that Gli3 controls the onset of cortical neurogenesis by determining the levels of Cdk6 expression, thereby regulating neuronal output and cortical size.

机译：脑皮质含有巨大数量的神经元，使其能够执行高度复杂的神经任务。了解这些神经元在正确的时间和地点以及准确的数字中如何构成主要挑战。在这里，我们在皮质神经发生中展示了一种用于皮质发育的关键调节剂的GLI3的新颖作用。我们表明神经元形成的发作延迟了GLI3条件小鼠突变体。基因表达分析和细胞循环测量表明，桡孔胶质细胞中G1和S阶段的缩短前后。降低的G1长度与细胞周期蛋白依赖性激酶基因CDK6的上调相关，其直接由GLI3调节。此外，对CDK6功能的药理干扰抵押GLI3突变体胚胎中的延迟神经发生。总的来说，我们的数据表明GLI3通过确定CDK6表达的水平来控制皮质神经发生的开始，从而调节神经元输出和皮质尺寸。

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来源
《Development》 |2018年第17期|共12页
作者
Hasenpusch-Theil Kerstin; West Stephen; Kelman Alexandra; Kozic Zrinko; Horrocks Sophie; McMahon Andrew P.; Price David J.; Mason Jason O.; Theil Thomas;
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作者单位

Univ Edinburgh Ctr Discovery Brain Sci Hugh Robson Bldg Edinburgh EH8 9XD Midlothian Scotland;

Univ Edinburgh Ctr Discovery Brain Sci Hugh Robson Bldg Edinburgh EH8 9XD Midlothian Scotland;

Univ Edinburgh Ctr Discovery Brain Sci Hugh Robson Bldg Edinburgh EH8 9XD Midlothian Scotland;

Univ Edinburgh Ctr Discovery Brain Sci Hugh Robson Bldg Edinburgh EH8 9XD Midlothian Scotland;

Univ Edinburgh Ctr Discovery Brain Sci Hugh Robson Bldg Edinburgh EH8 9XD Midlothian Scotland;

Univ Southern Calif WM Keck Sch Med Eli &

Edythe Brd CIRM Ctr Regenerat Med &

Stem Ce Dept Stem;

Univ Edinburgh Ctr Discovery Brain Sci Hugh Robson Bldg Edinburgh EH8 9XD Midlothian Scotland;

Univ Edinburgh Ctr Discovery Brain Sci Hugh Robson Bldg Edinburgh EH8 9XD Midlothian Scotland;

Univ Edinburgh Ctr Discovery Brain Sci Hugh Robson Bldg Edinburgh EH8 9XD Midlothian Scotland;

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原文格式 PDF
正文语种 eng
中图分类人体形态学;
关键词
Gli3; Neurogenesis; Cell cycle; Cdk6; Mouse;

机译：GLI3;神经发生;细胞周期;CDK6;鼠标;

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专利

1. Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression [J] . Hasenpusch-Theil Kerstin, West Stephen, Kelman Alexandra, Development . 2018,第17期

机译：通过CDK6表达调节径向胶质细胞周期，GLI3通过CDK6表达来控制皮质神经发生的开始
2. Kif11 dependent cell cycle progression in radial glial cells is required for proper neurogenesis in the zebrafish neural tube [J] . Kimberly Johnson, Chelsea Moriarty, Nessy Tania, Developmental biology . 2014,第1期

机译：斑马鱼神经管中适当的神经发生需要径向胶质细胞中Kif11依赖性细胞周期进程
3. The extracellular matrix, p53 and estrogen compete to regulate cell-surface Fas/Apo-1 suicide receptor expression in proliferating embryonic cerebral cortical precursors, and reciprocally, Fas-ligand modifies estrogen control of cell-cycle proteins [J] . Zulfiqar F Cheema, Daniel R Santillano, Stephen B Wade, BMC Neuroscience . 2004,第1期

机译：细胞外基质，p53和雌激素竞争性调节增殖的胚胎脑皮质前体中的细胞表面Fas / Apo-1自杀受体表达，相反，Fas-配体改变了雌激素对细胞周期蛋白的控制
4. Analysis of gene expression in glial cells exposed to radiofrequency electromagnetic fields using microarray [C] . Tomonori Sakurai, Eijiro Narita, Tomoko Kiyokawa, Meeting of the Bioelectromagnetics Society . 2010

机译：用微阵列暴露于射频电磁场的胶质细胞基因表达分析
5. Regulated ATF4 persistence in cell cycle control and neurogenesis [D] . Frank, Christopher Lee 2008

机译：调节ATF4在细胞周期控制和神经发生中的持久性
6. Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression [O] . Kerstin Hasenpusch-Theil, Stephen West, Alexandra Kelman, -1

机译：Gli3通过Cdk6表达调节星形胶质细胞周期从而控制皮质神经发生
7. Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression [O] . Kerstin Hasenpusch-Theil, Stephen West, Alexandra Kelman, 2018

机译：通过CDK6表达调节径向胶质细胞周期，GLI3通过CDK6表达来控制皮质神经发生的开始
8. Populations of Radial Glial Cells Respond Differently to Reelin and Neuregulin1 in a Ferret Model of Cortical Dysplasia [R] . 2010

机译：在皮质发育不良的雪貂模型中，桡神经胶质细胞群对Reelin和神经调节蛋白1的反应不同

Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression

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