title: Mecp2 regulates neural cell differentiation by suppressing the Id1 to Her2 axis in zebrafish.
abstract: Rett syndrome (RTT) is a progressive neurological disorder caused by mutations in the X-linked protein methyl-CpG-binding protein 2 (MeCP2). The endogenous function of MeCP2 during neural differentiation is still unclear. Here, we report that mecp2 is required for brain development in zebrafish. Mecp2 was broadly expressed initially in embryos and enriched later in the brain. Either morpholino knockdown or genetic depletion of mecp2 inhibited neuronal differentiation, whereas its overexpression promoted neuronal differentiation, suggesting an essential role of mecp2 in directing neural precursors into differentiated neurons. Mechanistically, her2 (the zebrafish ortholog of mammalian Hes5) was upregulated in mecp2 morphants in an Id1-dependent manner. Moreover, knockdown of either her2 or id1 fully rescued neuronal differentiation in mecp2 morphants. These results suggest that Mecp2 plays an important role in neural cell development by suppressing the Id1-Her2 axis, and provide new evidence that embryonic neural defects contribute to the later motor and cognitive dysfunctions in RTT.
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, China Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Gao
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Chang
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Shilin
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, China kphu@implad.ac.cn jingwei_xiong@pku.edu.cn.
authors.forename: Keping
authors.initials: K
authors.lastname: Hu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, China kphu@implad.ac.cn jingwei_xiong@pku.edu.cn.
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Xiong
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D018734:Genes, erbB-2; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D051798:Inhibitor of Differentiation Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051798:Inhibitor of Differentiation Protein 1; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D029961:Zebrafish Proteins
keywords: Her2; Hes5; Id1; Mecp2; Neuronal differentiation; Zebrafish