Functional roles of Otx2 transcription factor in postnatal mouse retinal development.
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.
Koike
Chieko
C
Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
Nishida
Akihiro
A
Ueno
Shinji
S
Saito
Hiromitsu
H
Sanuki
Rikako
R
Sato
Shigeru
S
Furukawa
Akiko
A
Aizawa
Shinichi
S
Matsuo
Isao
I
Suzuki
Noboru
N
Kondo
Mineo
M
Furukawa
Takahisa
T
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
D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D015534:Trans-Activators; C109288:cone rod homeobox protein; C045073:Cre recombinase; D019426:Integrases