An eIF4E1/4E-T Complex Determines the Genesis of Neurons from Precursors by Translationally Repressing a Proneurogenic Transcription Program
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Here, we have addressed the mechanisms that determine genesis of the correct numbers of neurons during development, focusing on the embryonic cortex. We identify in neural precursors a repressive complex involving eIF4E1 and its binding partner 4E-T that coordinately represses translation of proteins that determine neurogenesis. This eIF4E1/4E-T complex is present in granules with the processing body proteins Lsm1 and Rck, and disruption of this complex causes premature and enhanced neurogenesis and neural precursor depletion. Analysis of the 4E-T complex shows that it is highly enriched in mRNAs encoding transcription factors and differentiation-related proteins. These include the proneurogenic bHLH mRNAs, which colocalize with 4E-T in granules and whose protein products are aberrantly upregulated following knockdown of eIF4E, 4E-T, or processing body proteins. Thus, neural precursors are transcriptionally primed to generate neurons, but an eIF4E/4E-T complex sequesters and represses translation of proneurogenic proteins to determine appropriate neurogenesis.
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In vivo evidence has shown that normal expression and proper binding to EIF4E is required to maintain the correct balance.
“In vivo evidence has indeed shown that normal expression and proper binding to EIF4E is required to maintain the correct balance.77”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [77]
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- Authors
- Yang, G., Smibert, C. A., Kaplan, D. R., & Miller, F. D.
- Affiliations
- Hospital for Sick Children (CA)
- University of Toronto (CA)
- Corresponding author
- Kaplan, David R.
- Miller, Freda D.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 84
- Issue
- 4
- Pages
- 723-739
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2085367342
- Cited by
- 98
- References
- 30
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 13 · 2019: 10 · 2018: 3 · 2017: 10 · 2016: 10 · 2015: 8 · 2014: 1
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Canadian Institutes of Health Research (125945_1)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- eIF4E1, translation repression, neurogenesis, neuronal precursors, embryonic cortex, P-bodies, LSM1, bHLH transcription factors, neuronal differentiation, mRNA granules
- MeSH terms
- Animals, Humans, Neurons, Transcription, Genetic, Nucleocytoplasmic Transport Proteins, Eukaryotic Initiation Factor-4E, Mice, Neurogenesis, HEK293 Cells
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