Document Detail


Dicer is required for proliferation, viability, migration and differentiation in corticoneurogenesis.
MedLine Citation:
PMID:  22898830     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In mice, microRNAs (miRNAs) are required for embryonic viability, and previous reports implicate miRNA participation in brain cortical neurogenesis. Here, we provide a more comprehensive analysis of miRNA involvement in cortical brain development. To accomplish this we used mice in which Dicer, the RNase III enzyme necessary for canonical miRNA biogenesis, is depleted from Nestin-expressing progenitors and progeny cells. We systematically assessed how Dicer depletion impacts proliferation, cell death, migration and differentiation in the developing brain. Using markers for proliferation and in vivo labeling with thymidine analogs, we found reduced numbers of proliferating cells, and altered cell cycle kinetics from embryonic day 15.5 (E15.5). Progenitor cells were distributed aberrantly throughout the cortex rather than restricted to the ventricular and subventricular zones. Activated Caspase3 was elevated, reflecting increased cortical cell death as early as E15.5. Cajal-Retzius-positive cells were more numerous at E15.5 and were dysmorphic relative to control cortices. Consistent with this, Reelin levels were enhanced. Doublecortin and Rnd2 were also increased and showed altered distribution, supporting a strong regulatory role for miRNAs in both early and late neuronal migration. In addition, GFAP staining at E15.5 was more intense and disorganized throughout the cortex with Dicer depletion. These results significantly extend earlier works, and emphasize the impact of miRNAs on neural progenitor cell proliferation, apoptosis, migration, and differentiation in the developing mammalian brain.
Authors:
H S McLoughlin; S K Fineberg; L L Ghosh; L Tecedor; B L Davidson
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-13
Journal Detail:
Title:  Neuroscience     Volume:  223     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-24     Completed Date:  2013-05-01     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  285-95     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ltd.
Affiliation:
Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA 52240, USA.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Apoptosis / genetics
Bromodeoxyuridine
Cell Differentiation / genetics*
Cell Movement / genetics*
Cell Proliferation*
Cell Survival / genetics
Cerebral Cortex / cytology*,  embryology
DEAD-box RNA Helicases / genetics,  metabolism*
Embryo, Mammalian
Female
Humans
Ki-67 Antigen
Male
Mice
Nerve Tissue Proteins / genetics,  metabolism
Neurogenesis / genetics*
Pregnancy
RNA, Messenger
Ribonuclease III / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
DA025132/DA/NIDA NIH HHS; R21 DA025132/DA/NIDA NIH HHS; R25 GM058939/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Ki-67 Antigen; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 59-14-3/Bromodeoxyuridine; EC 3.1.26.3/Dicer1 protein, mouse; EC 3.1.26.3/Ribonuclease III; EC 3.6.1.-/DEAD-box RNA Helicases
Comments/Corrections

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