Targeted deletion of Dicer disrupts lens morphogenesis, corneal epithelium stratification, and whole eye development.
Dicer, a ribonuclease essential for miRNA processing, is expressed abundantly in developing mouse cornea and lens. We studied the roles of Dicer and miRNAs in eye development by conditionally deleting the Dicer gene in the mouse lens and corneal epithelium. Adult Dicer conditional null (DicerCN) mice had severe microphthalmia with no discernible lens and a poorly stratified corneal epithelium. Targeted deletion of Dicer effectively inhibited miRNA processing in the developing lens at 12.5 day of embryogenesis (E12.5). Lens development initiated normally but underwent progressive dystrophy between E14.5 and E18.5. Microarray analysis revealed activation of P53 signaling in DicerCN lenses at E13.5, consistent with increased apoptosis and reduced cell proliferation between E12.5 and E14.5. Expression of Pax6 and other lens developmental transcription factors were not greatly affected between E12.5 and E14.5 but decreased as the lens degenerated. Our data indicated an indispensible role for Dicer and miRNAs in lens and corneal development.
Li
Yan
Y
Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. liyan2@mail.nih.gov
Piatigorsky
Joram
J
D000818:Animals; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology*; D004722:Endoribonucleases / Q000235:genetics / Q000502:physiology*; D019573:Epithelium, Corneal / Q000196:embryology / Q000378:metabolism*; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III
D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
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