Loss of O-GlcNAc transferase in neural stem cells impairs corticogenesis
Loss of O-GlcNAc transferase in neural stem cells impairs corticogenesis
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神经干细胞中 O-GlcNAc 转移酶的缺失会损害皮质生成
DOI：
10.1016/j.bbrc.2020.08.084
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发表时间：
2020-11-19
影响因子：
3.1
通讯作者：
Wu, Haitao
中科院分区：
文献类型：
--
作者：
Cheng, Juanxian;Wu, Yan;Wu, Haitao
大脑皮层的正常发育对大脑的形成和功能至关重要。O-GlcNAc酰化是一种重要的翻译后修饰，调节神经元健康和神经退行性疾病中大脑皮层存活的关键途径。然而，在胚胎和出生后早期（0-21天）阶段，O-GlcNAc酰化在调节大脑皮层发育中的作用仍然是未知的。在这里，我们报告的选择性删除O-GlcNAc转移酶（OGT）在小鼠神经干细胞（NSCs）导致了一系列严重的脑发育缺陷，包括显着萎缩的皮质和海马组织结构，广泛的神经元凋亡，细胞增殖减少，诱导内质网（ER）的压力，并抑制神经元树突和轴突分化。OGT缺失导致的皮质生成障碍的病理机制可能在很大程度上依赖于复杂的生物学过程，如增殖、凋亡和分化。我们的研究结果表明，在神经干细胞的功能障碍O-GlcNAc酰化可能是一个重要的贡献者神经发育疾病。(C)2020爱思唯尔公司All rights reserved.
The proper development of the cerebral cortex is essential for brain formation and functioning. O-GlcNAcylation, an important posttranslational modification, regulates the pathways critical for neuronal health and the survival of the cerebral cortex in neurodegenerative diseases. However, the role of O-GlcNAcylation in regulating cerebral cortical development at the embryonic and early postnatal (0-21 days) stages is still largely unknown. Here we report that the selective deletion of O-GlcNAc transferase (OGT) in neural stem cells (NSCs) in mice led to a series of severe brain developmental deficits, including dramatic shrinkage of cortical and hippocampal histoarchitecture, widespread neuronal apoptosis, decrease in cell proliferation, induction of endoplasmic reticulum (ER) stress, and inhibition of neuronal dendritic and axonal differentiation. The pathology of corticogenesis deficits caused by OGT deletion may largely rely on complicated biological processes, such as proliferation, apoptosis and differentiation. Our results suggest that dysfunctional O-GlcNAcylation in NSCs may be an important contributor to neurodevelopmental diseases. (C) 2020 Elsevier Inc. All rights reserved.