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

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)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18997113
DOI: 10.1242/dev.025080

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
Watson School > Publications
Depositing User: Matt Covey
Date Deposited: 09 Jan 2013 16:53
Last Modified: 26 Sep 2014 18:55
PMCID: PMC2798592
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26449

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