title: Dicer plays essential roles for retinal development by regulation of survival and differentiation.
abstract: OBJECTIVE
  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.affiliation: Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Atsumi
authors.initials: A
authors.lastname: Iida
authors.forename: Toru
authors.initials: T
authors.lastname: Shinoe
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.forename: Sumiko
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D018274:Electroporation; D047108:Embryonic Development; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000378:metabolism / Q000473:pathology*; D010957:Plasmids; D012160:Retina / Q000196:embryology* / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology*; D043244:Ribonuclease III / Q000502:physiology*; D013234:Stem Cells / Q000473:pathology*
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases