title: Liver X receptor β delays transformation of radial glial cells into astrocytes during mouse cerebral cortical development.
abstract: Radial glial (RG) cells serve as stem cells to produce new born neurons and scaffolds for neuronal migration during corticogenesis. After neurogenesis and migration are completed, most RG cells transform into astrocytes. However, the mechanisms that determine how RG cells are transformed into astrocytes are not well understood. Using nestin as a specific marker for both RG cells and astrocytes, we found that loss of LXRβ caused a reduction in the level of RG fibers and increase in the astrocytes. At the same time, we showed that the level of brain lipid-binding protein (BLBP), a RG-specific protein, was lower in the LXRβ knockout (LXRβ(-/-)) mice than in the wild type (WT) littermates from E18.5 to P14, a time period when most of RG cells are transformed into astrocytes. However, loss of LXRβ induced significant increase in the number of GFAP labeled astrocytes in the cerebral cortex. An increase of the transformation of RG cells into astrocytes in LXRβ(-/-) mice was further confirmed by the increased percentage of BLBP and GFAP double stained cells in the total BLBP positive cells of the Layer I and Layers V-VI. TGF-β1 and Smad4 are thought to be involved in the transformation of RG cells into astrocytes. The expression levels of TGF-β1mRNA and Smad4 mRNA were significantly higher in the cerebral cortex of LXRβ(-/-) mice than that in the WT littermates at P2 and P7, but by P10 and P14, mRNA levels had normalized and no differences were observed between WT and LXRβ(-/-) mice. Taken together, our findings suggest that loss of LXRβ accelerates the transformation of RG cells into astrocytes and that this acceleration may be correlated to higher levels TGF-β1 and Smad4 in the cerebral cortex between P2 and P7.
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Immunology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Immunology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, University of Houston, TX 77054, United States; Division of Medical Nutrition, Department of Biosciences and Nutrition, Karolinska Institute, Novum 141 86, Sweden.
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.affiliation: Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. Electronic address: haiweixu2001@163.com.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, PR China. Electronic address: fanxiaotang2005@163.com.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin / Q000096:biosynthesis; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology*; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D000071518:Liver X Receptors; D009419:Nerve Tissue Proteins; D064231:Nestin; D057093:Orphan Nuclear Receptors
keywords: Astrocyte; Brain lipid-binding protein; Cerebral cortex; LXRβ; Radial glia; TGF-β1