title: Zebrafish Mecp2 is required for proper axonal elongation of motor neurons and synapse formation.
abstract: Rett syndrome is a severe neurodevelopmental disorder. It is caused by a mutation in methyl-CpG binding protein 2 (MecP2), a transcriptional regulator that recruits protein complexes involved in histone modification and chromatin remodeling. However, the role of Mecp2 in Rett syndrome remains unclear. In this study, we investigated the function of Mecp2 in neuronal development using zebrafish embryos. Mecp2 expression was detected ubiquitously in the central nervous system and muscles at 28 h postfertilization (hpf). We injected an antisense morpholino oligonucleotide (AMO) to induce Mecp2 knockdown phenotype. In mecp2 morphants (embryos with Mecp2 knockdown by AMO) at 28 and 72 hpf, we found an increase in abnormal axonal branches of caudal primary motor neurons and a decrease in motor activity. In mecp2 morphants at 24 hpf, we observed an increase in the expression of an mecp2 downstream candidate gene, brain derived neurotrophic factor (bdnf). In mecp2 morphants at 72 hpf, the presynaptic area stained by an anti-SV2 antibody was increased at the neuromuscular junction (NMJ). Interestingly, the size of SV2-positive presynaptic area at the NMJ was also increased following bdnf mRNA injection, while it was normalized in a double knockdown of mecp2 and bdnf. These results imply that Mecp2 is an important functional regulator of bdnf gene expression during neural circuit formation in zebrafish embryo. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1101-1113, 2017.
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nozawa
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kubodera
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan.
authors.forename: Hideomi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan.
authors.forename: Toshio
authors.identifier: 0000-0003-4931-7087
authors.initials: T
authors.lastname: Ohshima
mesh_terms: D000367:Age Factors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007814:Larva; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D000071446:Neuronal Outgrowth / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010812:Physical Stimulation; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D015027:Zebrafish
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051783:Methyl-CpG-Binding Protein 2; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D014404:Tubulin
keywords: Mecp2; axonal elongation; neuromuscular junction; zebrafish