title: Liver X receptor β is essential for the differentiation of radial glial cells to oligodendrocytes in the dorsal cortex.
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.
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, China.
authors.forename: P
authors.initials: P
authors.lastname: Xu
authors.affiliation: Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, China.
authors.forename: X
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, China.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, China.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Warner
authors.affiliation: 1] Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX, USA [2] Department of Biosciences and Nutrition, Karolinska Institute, Novum, Sweden.
authors.forename: J-A
authors.initials: JA
authors.lastname: Gustafsson
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, China.
authors.forename: X
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D002784:Cholesterol; D003337:Corpus Callosum / Q000502:physiology / Q000648:ultrastructure; D063928:Ependymoglial Cells / Q000166:cytology* / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D020547:Lateral Ventricles / Q000378:metabolism / Q000502:physiology; D000071518:Liver X Receptors; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D009900:Optic Nerve / Q000502:physiology / Q000648:ultrastructure; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides