title: COUP-TFI and -TFII nuclear receptors are expressed in amacrine cells and play roles in regulating the differentiation of retinal progenitor cells.
abstract: Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are members of the steroid/thyroid hormone receptor superfamily. We have shown that two homologous COUP-TF genes, COUP-TFI and COUP-TFII, are expressed in developing mouse retina with a unique gradient along the dorsal-ventral axis. In this work, we aimed to characterize the detailed expression patterns of COUP-TFs in mature retina. Their functions in retinal progenitor cell differentiation into subtypes of mature retinal cells were also examined. Immunostaining of frozen mouse retinal sections with antibodies against COUP-TFs and markers for retinal subtypes revealed that COUP-TFI and -TFII are expressed in amacrine cells, especially in a glycinergic subtype in mature mouse retina. Forced expression of COUP-TFI and -TFII in mouse retinal explant culture by retrovirus-mediated gene transfer promoted amacrine and cone photoreceptor cell differentiation, whereas that of rod photoreceptors decreased. Cell proliferation and apoptosis were not affected by the perturbation of COUP-TFI and -TFII expression levels. Using the Y79 retinoblastoma cell line, we observed that COUP-TFI and -TFII suppressed the transcriptional activation of the Nrl gene. We then analyzed one another member of COUP-TF transcription factors, COUP-TFgamma, whose structure is relatively distant from those of COUP-TFI and -TFII. It is expressed mainly in horizontal cells and has weak activity in inducing amacrine cells when COUP-TFgamma was ectopically expressed in retinal explants. In summary, we found that COUP-TFI and -TFII play roles in amacrine cell differentiation, and COUP-TFgamma has distinct expression pattern and roles during retinal development.
authors.affiliation: Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Inoue
authors.forename: Atsumi
authors.initials: A
authors.lastname: Iida
authors.forename: Shinya
authors.initials: S
authors.lastname: Satoh
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Sumiko
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D025042:Amacrine Cells / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D051838:COUP Transcription Factor I / Q000235:genetics*; D051837:COUP Transcription Factor II / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D005136:Eye Proteins / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids; D012160:Retina / Q000166:cytology*; D019572:Retinal Neoplasms / Q000235:genetics; D012175:Retinoblastoma / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D051838:COUP Transcription Factor I; D051837:COUP Transcription Factor II; D005136:Eye Proteins; C497590:Nr2f1 protein, mouse; C497587:Nr2f2 protein, mouse; C084884:Nrl protein, mouse