Tian, J.L.; Huang, C.-W.; Eslami, F.; Mannino, M.P.; Mai, R.L.; Hart, G.W. Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model. Cells2023, 12, 1520.
Tian, J.L.; Huang, C.-W.; Eslami, F.; Mannino, M.P.; Mai, R.L.; Hart, G.W. Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model. Cells 2023, 12, 1520.
Tian, J.L.; Huang, C.-W.; Eslami, F.; Mannino, M.P.; Mai, R.L.; Hart, G.W. Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model. Cells2023, 12, 1520.
Tian, J.L.; Huang, C.-W.; Eslami, F.; Mannino, M.P.; Mai, R.L.; Hart, G.W. Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model. Cells 2023, 12, 1520.
Abstract
The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia 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 cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons 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 cilia 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 cilia 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.
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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