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Obecks 差异表达控制血脑屏障的倍性。

Differential expression of Öbek controls ploidy in the blood-brain barrier.

机构信息

Institute of Neurobiology, University of Münster, Badestrasse 9, 48149 Münster, Germany.

Institute of Zoology, University of Cologne, Zülpicher Straße 47b, 50674 Cologne, Germany.

出版信息

Development. 2018 Aug 13;145(15):dev164111. doi: 10.1242/dev.164111.

Abstract

During development, tissue growth is mediated by either cell proliferation or cell growth, coupled with polyploidy. Both strategies are employed by the cell types that make up the blood-brain barrier. During larval growth, the perineurial glia proliferate, whereas the subperineurial glia expand enormously and become polyploid. Here, we show that the level of ploidy in the subperineurial glia is controlled by the N-terminal asparagine amidohydrolase homolog Öbek, and high Öbek levels are required to limit replication. In contrast, perineurial glia express moderate levels of Öbek, and increased Öbek expression blocks their proliferation. Interestingly, other dividing cells are not affected by alteration of Öbek expression. In glia, Öbek counteracts fibroblast growth factor and Hippo signaling to differentially affect cell growth and number. We propose a mechanism by which growth signals are integrated differentially in a glia-specific manner through different levels of Öbek protein to adjust cell proliferation versus endoreplication in the blood-brain barrier.

摘要

在发育过程中,组织生长是通过细胞增殖或细胞生长加上多倍体来介导的。构成血脑屏障的细胞类型都采用这两种策略。在幼虫生长过程中,神经周细胞胶质细胞增殖,而神经周细胞外胶质细胞则大量扩张并成为多倍体。在这里,我们表明,神经周细胞外胶质细胞的多倍体水平受 N 端天门冬酰胺酰胺水解酶同源物 Öbek 控制,需要高 Öbek 水平来限制复制。相比之下,神经周细胞胶质细胞表达中等水平的 Öbek,增加的 Öbek 表达会阻止其增殖。有趣的是,其他分裂细胞不受 Öbek 表达改变的影响。在神经胶质细胞中,Öbek 抵消了成纤维细胞生长因子和 Hippo 信号通路,从而以不同的方式影响细胞生长和数量。我们提出了一种机制,即通过不同水平的 Öbek 蛋白以特定于神经胶质细胞的方式差异整合生长信号,以调节血脑屏障中的细胞增殖与内复制。

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