PUBLICATION
Zebrafish Mecp2 is required for proper axonal elongation of motor neurons and synapse formation
- Authors
- Nozawa, K., Lin, Y., Kubodera, R., Shimizu, Y., Tanaka, H., Ohshima, T.
- ID
- ZDB-PUB-170404-4
- Date
- 2017
- Source
- Developmental Neurobiology 77(9): 1101-1113 (Journal)
- Registered Authors
- Ohshima, Toshio, Shimizu, Yuki, Tanaka, Hideomi
- Keywords
- none
- MeSH Terms
-
- Age Factors
- Animals
- Brain-Derived Neurotrophic Factor/metabolism
- Cell Differentiation
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/drug effects
- Gene Expression Regulation, Developmental/physiology*
- Larva
- Methyl-CpG-Binding Protein 2/genetics
- Methyl-CpG-Binding Protein 2/metabolism*
- Motor Activity/drug effects
- Motor Activity/physiology
- Motor Neurons/cytology*
- Motor Neurons/drug effects
- Neuromuscular Junction/drug effects
- Neuromuscular Junction/metabolism*
- Neuronal Outgrowth/drug effects
- Neuronal Outgrowth/physiology*
- Oligonucleotides, Antisense/pharmacology
- Physical Stimulation
- Presynaptic Terminals/drug effects
- Presynaptic Terminals/physiology
- RNA, Messenger/metabolism
- RNA, Messenger/pharmacology
- Tubulin/metabolism
- Zebrafish
- PubMed
- 28371371 Full text @ Dev. Neurobiol.
Citation
Nozawa, K., Lin, Y., Kubodera, R., Shimizu, Y., Tanaka, H., Ohshima, T. (2017) Zebrafish Mecp2 is required for proper axonal elongation of motor neurons and synapse formation. Developmental Neurobiology. 77(9):1101-1113.
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 hours post fertilization (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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping