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Liver X receptor β is essential for the differentiation of radial glial cells to oligodendrocytes in the dorsal cortex

Molecular Psychiatry volume 19, pages 947–957 (2014)Cite this article

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Abstract

Several psychiatric disorders are associated with aberrant white matter development, suggesting oligodendrocyte and myelin dysfunction in these diseases. There are indications that radial glial cells (RGCs) are involved in initiating myelination, and may contribute to the production of oligodendrocyte progenitor cells (OPCs) in the dorsal cortex. Liver X receptors (LXRs) are involved in maintaining normal myelin in the central nervous system (CNS), however, their function in oligodendrogenesis and myelination is not well understood. Here, we demonstrate that loss of LXRβ function leads to abnormality in locomotor activity and exploratory behavior, signs of anxiety and hypomyelination in the corpus callosum and optic nerve, providing in vivo evidence that LXRβ deletion delays both oligodendrocyte differentiation and maturation. Remarkably, along the germinal ventricular zone-subventricular zone and corpus callosum there is reduced OPC production from RGCs in LXRβ−/− mice. Conversely, in cultured RGC an LXR agonist led to increased differentiation into OPCs. Collectively, these results suggest that LXRβ, by driving RGCs to become OPCs in the dorsal cortex, is critical for white matter development and CNS myelination, and point to the involvement of LXRβ in psychiatric disorders.

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Acknowledgements

This study was supported by the National Nature Science Foundation of China (No. 31271051 and 81371197), Natural Science Foundation Project of CQ CSTC 2013jjB10028, the Swedish Research Council and a grant from the Robert A Welch Foundation (E-0004, J-ÅG).

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Author notes

  1. P Xu and H Xu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Histology and Embryology, Third Military Medical University, Chongqing, China

    P Xu, X Tang, L Xu, Y Wang, L Guo, Z Yang & X Fan

  2. Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, Chongqing, China

    H Xu

  3. Institute of Immunology, PLA, Third Military Medical University, Chongqing, China

    Y Xing & Y Wu

  4. Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX, USA

    M Warner & J-A Gustafsson

  5. Department of Biosciences and Nutrition, Karolinska Institute, Novum, Sweden

    J-A Gustafsson

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Correspondence to J-A Gustafsson or X Fan.

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Xu, P., Xu, H., Tang, X. et al. Liver X receptor β is essential for the differentiation of radial glial cells to oligodendrocytes in the dorsal cortex. Mol Psychiatry 19, 947–957 (2014). https://doi.org/10.1038/mp.2014.60

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