miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex
Open accessAbstract
Neurogenesis during the development of the mammalian cerebral cortex involves a switch of neural stem and progenitor cells from proliferation to differentiation. To explore the possible role of microRNAs (miRNAs) in this process, we conditionally ablated Dicer in the developing mouse neocortex using Emx1-Cre, which is specifically expressed in the dorsal telencephalon as early as embryonic day (E) 9.5. Dicer ablation in neuroepithelial cells, which are the primary neural stem and progenitor cells,and in the neurons derived from them, was evident from E10.5 onwards, as ascertained by the depletion of the normally abundant miRNAs miR-9and miR-124. Dicer ablation resulted in massive hypotrophy of the postnatal cortex and death of the mice shortly after weaning. Analysis of the cytoarchitecture of the Dicer-ablated cortex revealed a marked reduction in radial thickness starting at E13.5, and defective cortical layering postnatally. Whereas the former was due to neuronal apoptosis starting at E12.5, which was the earliest detectable phenotype, the latter reflected dramatic impairment of neuronal differentiation. Remarkably, the primary target cells of Dicer ablation, the neuroepithelial cells, and the neurogenic progenitors derived from them, were unaffected by miRNA depletion with regard to cell cycle progression, cell division, differentiation and viability during the early stage of neurogenesis, and only underwent apoptosis starting at E14.5. Our results support the emerging concept that progenitors are less dependent on miRNAs than their differentiated progeny, and raise interesting perspectives as to the expansion of somatic stem cells.
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The link between miRNAs and the pathophysiology of depression may be implicated by the fact that miRNAs regulate neuronal regulation, neurotransmitter regulation, and microglia activation.
“The link between miRNAs and the pathophysiology of depression248–252 may be implicated by the fact that miRNAs regulate neuronal regulation, neurotransmitter regulation, and microglia activation.253,254”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [253]
The Discussion (page not provided) reports evidence that miRNAs are required for neuronal differentiation in the developing mouse cortex. The cited paper does not establish the other mechanisms attributed to citations 253–254: neurotransmitter regulation or microglial activation. The depression link is attached to different citations. (LLM, conf=0.86)
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- Authors
- De Pietri Tonelli, D., Pulvers, J. N., Haffner, C., Murchison, E. P., Hannon, G. J., & Huttner, W. B.
- Affiliations
- Max-Planck Institute of Molecular Cell Biology and Genetics,Pfotenhauerstrasse 108, 01307 Dresden, Germany.
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Howard Hughes Medical Institute (US)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2008-12-01
- Volume
- 135
- Issue
- 23
- Pages
- 3911-3921
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2798592
- OpenAlex
- W2145160583
- Cited by
- 343
- References
- 50
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 17 · 2020: 14 · 2019: 15 · 2018: 9 · 2017: 22 · 2016: 28 · 2015: 22 · 2014: 33 · 2013: 45 · 2012: 33
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Cancer Institute (P01CA013106)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- microRNA, Dicer, neurogenesis, embryonic neocortex, neural progenitor cells, neuroepithelial cells, neuronal differentiation, neuronal apoptosis, cortical lamination, miR-9, miR-124, adult stem cells
- MeSH terms
- Animals, Animals, Newborn, Cell Count, Cell Differentiation, Cell Survival, Embryo, Mammalian, Endoribonucleases, Interneurons, Mitosis, Neurons, Stem Cells, Apoptosis, Gene Deletion, Gene Expression Regulation, Developmental, Cell Lineage, Neocortex, MicroRNAs, Ribonuclease III, Embryonic Development, Cell Proliferation, Mice, DEAD-box RNA Helicases, Neurogenesis
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