Ogt-mediated O-GlcNAcylation is enriched in the nervous system and involves in neuronal development, brain function and neurological diseases. However, the roles of Ogt and O-GlcNAcylation in embryonic neurogenesis have remained largely unknown. Here, we show that Ogt is highly expressed in embryonic brain, and Ogt depletion reduces the proliferation of embryonic neural stem cells and migration of new born neurons. Ogt depletion in cultured hippocampal neurons impairs neuronal maturation, including reduced dendritic numbers and length, and immature development of spines. Mechanistically, Ogt depletion decreases the activity of Wnt/β-catenin signaling. Ectopic β-catenin rescues neuronal developmental deficits caused by Ogt depletion. Ogt also regulates human cortical neurogenesis in forebrain organoids derived from induced pluripotent stem cells. Our findings reveal the essential roles and mechanisms of Ogt-mediated O-GlcNAc modification in regulating mammalian neuronal development.

中文翻译：

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O-GlcNAc 转移酶 Ogt 通过调节 Wnt/β-catenin 信号传导调节胚胎神经元发育

Ogt 介导的 O-GlcNAcylation 在神经系统中富集，并涉及神经元发育、脑功能和神经系统疾病。然而，Ogt 和 O-GlcNAcylation 在胚胎神经发生中的作用仍然很大程度上未知。在这里，我们表明 Ogt 在胚胎脑中高度表达，并且 Ogt 消耗减少了胚胎神经干细胞的增殖和新生神经元的迁移。培养的海马神经元中的 Ogt 消耗会损害神经元成熟，包括减少的树突数量和长度，以及脊柱的不成熟发育。从机制上讲，Ogt 消耗降低了 Wnt/β-catenin 信号传导的活性。异位 β-连环蛋白可挽救由 Ogt 耗竭引起的神经元发育缺陷。Ogt 还调节源自诱导多能干细胞的前脑类器官中的人类皮质神经发生。