A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors
| العنوان: | A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors |
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| المؤلفون: | Derrick J. Reynolds, Colleen McSweeney, Jun Zhu, Yijing Zhou, Yongsheng Shi, Fengping Dong, Jizhong Zou, Donghua Zou, Dazhi Deng, Yingwei Mao, Aswathy Sebastian, Long Liu, Istvan Albert, Yonggang Wang |
| المصدر: | Neural Development Neural development, vol 10, iss 1 Zou, D; McSweeney, C; Sebastian, A; Reynolds, DJ; Dong, F; Zhou, Y; et al.(2015). A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors. Neural Development. doi: 10.1186/s13064-015-0045-7. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/9vt68245 |
| بيانات النشر: | BioMed Central, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Cellular differentiation, Autism, Nonsense-mediated decay, Neurodevelopment, Stem Cell Research - Embryonic - Non-Human, Inbred C57BL, Medical and Health Sciences, Mice, Neural Stem Cells, 2.1 Biological and endogenous factors, Developmental, Aetiology, RNA, Small Interfering, Cells, Cultured, Genetics, Regulation of gene expression, Pediatric, Gene knockdown, Microscopy, Cultured, Microscopy, Confocal, Neurogenesis, Brain, Gene Expression Regulation, Developmental, RNA-Binding Proteins, Cell Differentiation, Biological Sciences, Immunohistochemistry, Neural stem cell, Cell biology, medicine.anatomical_structure, Mental Health, Confocal, Neurological, Nonsense mediated mRNA decay, Research Article, Cells, Intellectual and Developmental Disabilities (IDD), 1.1 Normal biological development and functioning, Immunoblotting, Subventricular zone, Biology, Small Interfering, Transfection, RBM8a, Developmental Neuroscience, Underpinning research, medicine, Animals, Humans, Neural progenitor cells, Cell Proliferation, Neurosciences, Stem Cell Research, Brain Disorders, Exon junction complex, Mice, Inbred C57BL, Gene Expression Regulation, RNA, Psychiatric disorders, Developmental Biology |
| الوصف: | Background Nonsense mediated mRNA decay (NMD) is an RNA surveillance mechanism that controls RNA stability and ensures the speedy degradation of erroneous and unnecessary transcripts. This mechanism depends on several core factors in the exon junction complex (EJC), eIF4A3, RBM8a, Magoh, and BTZ, as well as peripheral factors to distinguish premature stop codons (PTCs) from normal stop codons in transcripts. Recently, emerging evidence has indicated that NMD factors are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). However, the mechanism in which these factors control embryonic brain development is not clear. Result We found that RBM8a is critical for proliferation and differentiation in cortical neural progenitor cells (NPCs). RBM8a is highly expressed in the subventricular zone (SVZ) of the early embryonic cortex, suggesting that RBM8a may play a role in regulating NPCs. RBM8a overexpression stimulates embryonic NPC proliferation and suppresses neuronal differentiation. Conversely, knockdown of RBM8a in the neocortex reduces NPC proliferation and promotes premature neuronal differentiation. Moreover, overexpression of RBM8a suppresses cell cycle exit and keeps cortical NPCs in a proliferative state. To uncover the underlying mechanisms of this phenotype, genome-wide RNAseq was used to identify potential downstream genes of RBM8a in the brain, which have been implicated in autism and neurodevelopmental disorders. Interestingly, autism and schizophrenia risk genes are highly represented in downstream transcripts of RBM8a. In addition, RBM8a regulates multiple alternative splicing genes and NMD targets that are implicated in ASD. Taken together, this data suggests a novel role of RBM8a in the regulation of neurodevelopment. Conclusions Our studies provide some insight into causes of mental illnesses and will facilitate the development of new therapeutic strategies for neurodevelopmental illnesses. Electronic supplementary material The online version of this article (doi:10.1186/s13064-015-0045-7) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1749-8104 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ffadb077215c0253886bb8b5f6c72810 http://europepmc.org/articles/PMC4479087 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ffadb077215c0253886bb8b5f6c72810 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17498104 |
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