title: Functional roles of Otx2 transcription factor in postnatal mouse retinal development.
abstract: We previously reported that Otx2 is essential for photoreceptor cell fate determination; however, the functional role of Otx2 in postnatal retinal development is still unclear although it has been reported to be expressed in retinal bipolar cells and photoreceptors at postnatal stages. In this study, we first examined the roles of Otx2 in the terminal differentiation of photoreceptors by analyzing Otx2; Crx double-knockout mice. In Otx2+/-; Crx-/- retinas, photoreceptor degeneration and downregulation of photoreceptor-specific genes were much more prominent than in Crx-/- retinas, suggesting that Otx2 has a role in the terminal differentiation of the photoreceptors. Moreover, bipolar cells decreased in the Otx2+/-; Crx-/- retina, suggesting that Otx2 is also involved in retinal bipolar-cell development. To further investigate the role of Otx2 in bipolar-cell development, we generated a postnatal bipolar-cell-specific Otx2 conditional-knockout mouse line. Immunohistochemical analysis of this line showed that the expression of protein kinase C, a marker of mature bipolar cells, was significantly downregulated in the retina. Electroretinograms revealed that the electrophysiological function of retinal bipolar cells was impaired as a result of Otx2 ablation. These data suggest that Otx2 plays a functional role in the maturation of retinal photoreceptor and bipolar cells.
authors.affiliation: Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Koike
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nishida
authors.forename: Shinji
authors.initials: S
authors.lastname: Ueno
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Saito
authors.forename: Rikako
authors.initials: R
authors.lastname: Sanuki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.forename: Akiko
authors.initials: A
authors.lastname: Furukawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aizawa
authors.forename: Isao
authors.initials: I
authors.lastname: Matsuo
authors.forename: Noboru
authors.initials: N
authors.lastname: Suzuki
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002452:Cell Count; D002454:Cell Differentiation; D002470:Cell Survival; D002999:Clone Cells; D004596:Electroretinography; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009928:Organ Specificity; D051857:Otx Transcription Factors / Q000378:metabolism*; D010641:Phenotype; D010786:Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000378:metabolism; D012190:Retroviridae; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D015534:Trans-Activators; C109288:cone rod homeobox protein; C045073:Cre recombinase; D019426:Integrases