Essential role of the nuclear isoform of RBFOX1, a candidate gene for autism spectrum disorders, in the brain development
Open accessAbstract
Gene abnormalities in RBFOX1, encoding an mRNA-splicing factor, have been shown to cause autism spectrum disorder and other neurodevelopmental disorders. Since pathophysiological significance of the dominant nuclear isoform in neurons, RBFOX1-isoform1 (iso1), remains to be elucidated, we performed comprehensive analyses of Rbfox1-iso1 during mouse corticogenesis. Knockdown of Rbfox1-iso1 by in utero electroporation caused abnormal neuronal positioning during corticogenesis, which was attributed to impaired migration. The defects were found to occur during radial migration and terminal translocation, perhaps due to impaired nucleokinesis. Axon extension and dendritic arborization were also suppressed in vivo in Rbfox1-iso1-deficient cortical neurons. In addition, electrophysiology experiments revealed significant defects in the membrane and synaptic properties of the deficient neurons. Aberrant morphology was further confirmed by in vitro analyses; Rbfox1-iso1-konckdown in hippocampal neurons resulted in the reduction of primary axon length, total length of dendrites, spine density and mature spine number. Taken together, this study shows that Rbfox1-iso1 plays an important role in neuronal migration and synapse network formation during corticogenesis. Defects in these critical processes may induce structural and functional defects in cortical neurons, and consequently contribute to the pathophysiology of neurodevelopmental disorders with RBFOX1 abnormalities.
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Knockdown and silencing of RBFOX1 during mouse corticogenesis impairs neuronal migration and synapse formation.
“Knockdown and silencing of RBFOX1 during mouse corticogenesis impairs neuronal migration and synapse formation (Hamada et al., 2015; Hamada et al., 2016)”
From Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders (2019) · cites this paper as Hamada et al., 2016
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Sorted by citations
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
Lee, P. H., Anttila, V., Won, H., Feng, Y.-C. A., Rosenthal, J., Zhu, Z., Tucker-Drob, E. M., Nivard, M. G., Grotzinger, A. D., Posthuma, D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.11.020 · Cited by 1,381 · see citing works
“Knockdown and silencing of RBFOX1 during mouse corticogenesis impairs neuronal migration and synapse formation (Hamada et al., 2015; Hamada et al., 2016), implying its pivotal role in early cortical maturation.”
BackgroundRNA‐PROTACs: Degraders of RNA‐Binding Proteins
Ghidini, A., Cléry, A., Halloy, F., Allain, F. H. T., & Hall, J. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202012330 · Cited by 197 · see citing works
- Authors
- Hamada, N., Ito, H., Nishijo, T., Iwamoto, I., Morishita, R., Tabata, H., Momiyama, T., & Nagata, K.-I.
- Affiliations
- Japan Society for the Promotion of Science (JP)
- Aichi Human Service Center (JP)
- Jikei University School of Medicine (JP)
- Corresponding author
- Nagata, Koh-Ichi
- Venue
- Scientific Reports
- Published
- 2016-08-02
- Volume
- 6
- Issue
- 1
- Pages
- 30805-30805
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4969621
- OpenAlex
- W2476212429
- Cited by
- 86
- References
- 10
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 18 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 17 · 2019: 11 · 2018: 6 · 2017: 7 · 2016: 1
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development (15ek0109040h0002)
- Ministry of Education, Culture, Sports, Science and Technology (25122722, 25670488, 24390271)
- Japan Society for the Promotion of Science (16K07037, 25430046, 16K08264, 25461658, 15K15399)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- RBFOX1, autism spectrum disorder, cortical development, neuronal migration, radial migration, axon growth, dendritic branching, dendritic spines, synaptic function, mRNA splicing, neurodevelopmental disorders, hippocampal neurons
- MeSH terms
- Autism Spectrum Disorder, RNA Splicing Factors, Animals, Axons, Brain, Cell Movement, Cell Nucleus, Cells, Cultured, Humans, Neuronal Plasticity, Neurons, Protein Isoforms, Mice, Neurogenesis, Gene Knockout Techniques
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