Nr2e1 Downregulation Is Involved in Excess Retinoic Acid-induced Developmental Abnormality in the Mouse Brain.

Juan YU; Qian Guo; Jian Bing MU; Ting Zhang; Ren Ke LI; Jun Xie

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Nr2e1 Downregulation Is Involved in Excess Retinoic Acid-induced Developmental Abnormality in the Mouse Brain.

Author: Juan YU ¹ ; Qian GUO ¹ ; Jian Bing MU ² ; Ting ZHANG ³ ; Ren Ke LI ⁴ ; Jun XIE ¹
Author Information

1. Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
3. Capital Institute of Pediatrics, Beijing 100020, China.
4. Division of Cardiovascular Surgery and Toronto General Research Institute, University Health Network, Toronto M3J 1P3, Canada.
Publication Type:Journal Article
Keywords: Brain abnormality; Neural stem cells; Nr2e1 gene; Retinoic acid
MeSH: Animals; Brain; cytology; embryology; Cell Proliferation; Down-Regulation; Gene Expression Regulation; Gene Expression Regulation, Developmental; drug effects; Mice; Mice, Inbred C57BL; Neural Stem Cells; drug effects; physiology; Receptors, Cytoplasmic and Nuclear; genetics; metabolism; Tretinoin; pharmacology
From: Biomedical and Environmental Sciences 2017;30(3):185-193
CountryChina
Language:English
Abstract:
OBJECTIVEThis study aimed to investigate the expression pattern and function of Nuclear receptor subfamily 2 group E member 1 (Nr2e1) in retinoic acid (RA)-induced brain abnormality.
METHODSThe mouse model of brain abnormality was established by administering 28 mg/kg RA, and neural stem cells (NSCs) were isolated from the mouse embryo and cultured in vitro. Nr2e1 expression was detected by whole mount in situ hybridization, RT-PCR, and Western blotting. Nr2e1 function was determined by transducing Nr2e1 shRNA into NSCs, and the effect on the sonic hedgehog (Shh) signaling pathway was assessed in the cells. In addition, the regulation of Nr2e1 expression by RA was also determined in vitro.
RESULTSNr2e1 expression was significantly downregulated in the brain and NSCs of RA-treated mouse embryos, and knockdown of Nr2e1 affected the proliferation of NSCs in vitro. In addition, a similar expression pattern of Nr2e1 and RA receptor (RAR) α was observed after treatment of NSCs with different concentrations of RA.
CONCLUSIONOur study demonstrated that Nr2e1 could be regulated by RA, which would aid a better understanding of the mechanism underlying RA-induced brain abnormality.