PMID- 28371371 OWN - NLM STAT- MEDLINE DCOM- 20180430 LR - 20180617 IS - 1932-846X (Electronic) IS - 1932-8451 (Linking) VI - 77 IP - 9 DP - 2017 Sep TI - Zebrafish Mecp2 is required for proper axonal elongation of motor neurons and synapse formation. PG - 1101-1113 LID - 10.1002/dneu.22498 [doi] AB - 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. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1101-1113, 2017. CI - (c) 2017 Wiley Periodicals, Inc. FAU - Nozawa, Keisuke AU - Nozawa K AD - Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan. FAU - Lin, Yanbin AU - Lin Y AD - Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan. FAU - Kubodera, Ryota AU - Kubodera R AD - Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan. FAU - Shimizu, Yuki AU - Shimizu Y AD - Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan. FAU - Tanaka, Hideomi AU - Tanaka H AD - Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan. FAU - Ohshima, Toshio AU - Ohshima T AUID- ORCID: 0000-0003-4931-7087 AD - Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, 162-8480, Japan. LA - eng PT - Journal Article DEP - 20170424 PL - United States TA - Dev Neurobiol JT - Developmental neurobiology JID - 101300215 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Methyl-CpG-Binding Protein 2) RN - 0 (Oligonucleotides, Antisense) RN - 0 (RNA, Messenger) RN - 0 (Tubulin) SB - IM MH - Age Factors MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Differentiation MH - Embryo, Nonmammalian MH - Gene Expression Regulation, Developmental/drug effects/*physiology MH - Larva MH - Methyl-CpG-Binding Protein 2/genetics/*metabolism MH - Motor Activity/drug effects/physiology MH - Motor Neurons/*cytology/drug effects MH - Neuromuscular Junction/drug effects/*metabolism MH - Neuronal Outgrowth/drug effects/*physiology MH - Oligonucleotides, Antisense/pharmacology MH - Physical Stimulation MH - Presynaptic Terminals/drug effects/physiology MH - RNA, Messenger/metabolism/pharmacology MH - Tubulin/metabolism MH - Zebrafish OTO - NOTNLM OT - Mecp2 OT - axonal elongation OT - neuromuscular junction OT - zebrafish EDAT- 2017/04/04 06:00 MHDA- 2018/05/01 06:00 CRDT- 2017/04/04 06:00 PHST- 2016/11/11 00:00 [received] PHST- 2017/03/08 00:00 [revised] PHST- 2017/03/23 00:00 [accepted] PHST- 2017/04/04 06:00 [pubmed] PHST- 2018/05/01 06:00 [medline] PHST- 2017/04/04 06:00 [entrez] AID - 10.1002/dneu.22498 [doi] PST - ppublish SO - Dev Neurobiol. 2017 Sep;77(9):1101-1113. doi: 10.1002/dneu.22498. Epub 2017 Apr 24.