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- Title
Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model.
- Authors
Tian, Jie L.; Huang, Chia-Wei; Eslami, Farzad; Mannino, Michael Philip; Mai, Rebecca Lee; Hart, Gerald W.
- Abstract
The primary cilium plays critical roles in the homeostasis and development of neurons. Recent studies demonstrate that cilium length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilium length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilium length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilium length increased significantly during maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilium length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilium length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.
- Subjects
NEURON development; CILIA &; ciliary motion; NEURAL stem cells; PLURIPOTENT stem cells; DEVELOPMENTAL neurobiology; CELL cycle; INSULIN sensitivity
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 11, p1520
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12111520