O-GlcNAc transferase Ogt regulates embryonic neuronal development through modulating Wnt/β-catenin signaling

Shen, Hui; Zhao, Xingsen; Chen, Junchen; Qu, Wenzheng; Huang, Xiaoli; Wang, Mengxuan; Shao, Zhiyong; Shu, Qiang; Li, Xuekun

doi:10.1093/hmg/ddab223

O-GlcNAc transferase Ogt regulates embryonic neuronal development through modulating Wnt/β-catenin signaling

Journal Article · Wed Aug 04 00:00:00 EDT 2021 · Human Molecular Genetics

DOI:https://doi.org/10.1093/hmg/ddab223· OSTI ID:1836347

Shen, Hui; Zhao, Xingsen; Chen, Junchen; Qu, Wenzheng; Huang, Xiaoli; Wang, Mengxuan; Shao, Zhiyong; Shu, Qiang;

Abstract

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.

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Sponsoring Organization:: USDOE Office of Electricity (OE), Advanced Grid Research & Development. Power Systems Engineering Research

OSTI ID:: 1836347

Journal Information:: Human Molecular Genetics, Journal Name: Human Molecular Genetics Journal Issue: 1 Vol. 31; ISSN 0964-6906

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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