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细胞内控制中间神经元迁移驱动皮层形态发生。

Cell-Intrinsic Control of Interneuron Migration Drives Cortical Morphogenesis.

机构信息

GIGA-Neurosciences, University of Liège, C.H.U. Sart Tilman, Liège 4000, Belgium.

Center for Brain and Cognition, Department of Information and Technology, Universitat Pompeu Fabra, Calle Ramon Trias Fargas 25-27, Barcelona 08005, Spain.

出版信息

Cell. 2018 Feb 22;172(5):1063-1078.e19. doi: 10.1016/j.cell.2018.01.031.

Abstract

Interneurons navigate along multiple tangential paths to settle into appropriate cortical layers. They undergo a saltatory migration paced by intermittent nuclear jumps whose regulation relies on interplay between extracellular cues and genetic-encoded information. It remains unclear how cycles of pause and movement are coordinated at the molecular level. Post-translational modification of proteins contributes to cell migration regulation. The present study uncovers that carboxypeptidase 1, which promotes post-translational protein deglutamylation, controls the pausing of migrating cortical interneurons. Moreover, we demonstrate that pausing during migration attenuates movement simultaneity at the population level, thereby controlling the flow of interneurons invading the cortex. Interfering with the regulation of pausing not only affects the size of the cortical interneuron cohort but also impairs the generation of age-matched projection neurons of the upper layers.

摘要

中间神经元沿着多条切线路径行进,以定居在适当的皮质层中。它们经历间歇性核跳跃驱动的跳跃式迁移,其调节依赖于细胞外线索和遗传编码信息之间的相互作用。目前尚不清楚分子水平上如何协调暂停和运动的循环。蛋白质的翻译后修饰有助于细胞迁移的调节。本研究揭示了羧肽酶 1(可促进翻译后蛋白质脱谷氨酰胺作用)控制着迁移皮质中间神经元的暂停。此外,我们证明了迁移过程中的暂停会减弱群体水平上的运动同步性,从而控制中间神经元侵入皮质的流动。干扰暂停的调节不仅会影响皮质中间神经元群体的大小,还会损害上层年龄匹配的投射神经元的产生。

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