Document Detail


Dicer plays essential roles for retinal development by regulation of survival and differentiation.
MedLine Citation:
PMID:  21273552     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Much attention has been paid to the roles of microRNA in developmental and biological processes. Dicer plays essential roles in cell survival and proliferation in various organs. We examined the role of Dicer in retinal development using retina-specific conditional knockout of Dicer in mice.
METHODS: Dkk3-Cre expressed the Cre gene in retinal progenitor cells from an early embryonic stage. The authors analyzed Dkk-Cre/Dicer-flox (Dicer-CKO) mice for their survival, proliferation, and differentiation. To analyze the role of Dicer in later stages of retinal development, a Cre expression plasmid was introduced into the neonatal retina by electroporation, and retinal differentiation was examined.
RESULTS: Dicer-CKO mice were born at the numbers we expected, based on Mendelian genetics, but their eyes never opened. Massive death of retinal progenitor cells occurred during embryogenesis, resulting in microphthalmia, and most retinal cells had disappeared by postnatal day 14. In vitro reaggregation culture of Dicer-CKO retinal cells showed that cell death and the suppression of proliferation by Dicer inactivation occurred in a cell-autonomous manner. Cell differentiation markers were expressed in the Dicer-CKO retina; however, these cells localized abnormally, and the inner plexiform layer was absent, suggesting that cell migration and morphologic differentiation, especially process extension, were perturbed. Forced neonatal expression of Cre induced apoptosis and affected the expression of differentiation markers.
CONCLUSIONS: Taken together, these results show that Dicer is essential during early retinal development.
Authors:
Atsumi Iida; Toru Shinoe; Yukihiro Baba; Hiroyuki Mano; Sumiko Watanabe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-05-06
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  52     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-09     Completed Date:  2011-07-21     Revised Date:  2013-01-09    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3008-17     Citation Subset:  IM    
Affiliation:
Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation*
Cell Proliferation
Cell Survival
Cells, Cultured
DEAD-box RNA Helicases / physiology*
Electroporation
Embryonic Development
Gene Deletion
Green Fluorescent Proteins / genetics
Mice
Mice, Inbred ICR
Mice, Knockout
Mice, Transgenic
Microphthalmos / metabolism,  pathology*
Plasmids
Retina / embryology*,  pathology
Retinal Degeneration / metabolism,  pathology*
Ribonuclease III / physiology*
Stem Cells / pathology*
Chemical
Reg. No./Substance:
0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins; EC 3.1.26.3/Dicer1 protein, mouse; EC 3.1.26.3/Ribonuclease III; EC 3.6.1.-/DEAD-box RNA Helicases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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