De Pietri Tonelli, D., Pulvers, J. N., Haffner, C., Murchison, E. P., Hannon, G. J., Huttner, W. B.
(2008)
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.
Development, 135 (23).
pp. 3911-3921.
ISSN 09501991 (ISSN)
Abstract
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-9 and 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.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
Dicer (Dicer 1) knockout
MicroRNAs
Neurogenesis
dicer
microRNA
DEAD box protein
Dicer1 protein, mouse
ribonuclease
unclassified drug
animal cell
animal tissue
apoptosis
article
brain cortex atrophy
cell survival
controlled study
embryo
enzyme inhibition
gene function
gene repression
mortality
mouse
neocortex
nerve cell
nerve cell differentiation
nervous system development
neuroepithelium
newborn
nonhuman
postnatal development
priority journal
stem cell
animal
animal embryo
cell count
cell differentiation
cell lineage
cell proliferation
cytology
embryo development
enzymology
gene deletion
gene expression regulation
genetics
interneuron
metabolism
mitosis
prenatal development
Mammalia
Mus
Animals
Animals, Newborn
DEAD-box RNA Helicases
Embryo, Mammalian
Embryonic Development
Endoribonucleases
Gene Expression Regulation, Developmental
Interneurons
Mice
Neurons
Stem Cells |
| Subjects: |
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
organs, tissues, organelles, cell types and functions > organs types and functions > brain
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > tissues types and functions > cerebral cortex
organism description > animal > developmental stage > embryo
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Hannon lab
School of Biological Sciences > Publications |
| Depositing User: |
Matt Covey
|
| Date: |
2008 |
| Date Deposited: |
09 Jan 2013 16:53 |
| Last Modified: |
26 Sep 2014 18:55 |
| PMCID: |
PMC2798592 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/26449 |
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