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Dicer Plays Essential Roles for Retinal Development by Regulation of Survival and Differentiation
- Source :
- Investigative Opthalmology & Visual Science. 52:3008
- Publication Year :
- 2011
- Publisher :
- Association for Research in Vision and Ophthalmology (ARVO), 2011.
-
Abstract
- 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.
- Subjects :
- Ribonuclease III
Cell Survival
Cellular differentiation
Green Fluorescent Proteins
genetic processes
Embryonic Development
Mice, Transgenic
Biology
Retina
DEAD-box RNA Helicases
Mice
chemistry.chemical_compound
Conditional gene knockout
medicine
Animals
Microphthalmos
Cells, Cultured
Cell Proliferation
Mice, Knockout
Mice, Inbred ICR
Early embryonic stage
Stem Cells
Retinal Degeneration
fungi
food and beverages
Cell Differentiation
Retinal
Inner plexiform layer
Cell biology
enzymes and coenzymes (carbohydrates)
Electroporation
medicine.anatomical_structure
chemistry
biology.protein
Stem cell
Gene Deletion
Plasmids
Dicer
Subjects
Details
- ISSN :
- 15525783
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Investigative Opthalmology & Visual Science
- Accession number :
- edsair.doi.dedup.....39eea87c0244bbebd73eb6026e1118de