title: Otx2 is involved in the regional specification of the developing retinal pigment epithelium by preventing the expression of sox2 and fgf8, factors that induce neural retina differentiation.
abstract: The retinal pigment epithelium (RPE) shares its developmental origin with the neural retina (NR). When RPE development is disrupted, cells in the presumptive RPE region abnormally differentiate into NR-like cells. Therefore, the prevention of NR differentiation in the presumptive RPE area seems to be essential for regionalizing the RPE during eye development. However, its molecular mechanisms are not fully understood. In this study, we conducted a functional inhibition of a transcription factor Otx2, which is required for RPE development, using early chick embryos. The functional inhibition of Otx2 in chick eyes, using a recombinant gene encoding a dominant negative form of Otx2, caused the outer layer of the optic cup (the region forming the RPE, when embryos normally develop) to abnormally form an ectopic NR. In that ectopic NR, the characteristics of the RPE did not appear and NR markers were ectopically expressed. Intriguingly, the repression of Otx2 function also caused the ectopic expression of Fgf8 and Sox2 in the outer layer of the optic cup (the presumptive RPE region of normally developing eyes). These two factors are known to be capable of inducing NR cell differentiation in the presumptive RPE region, and are not expressed in the normally developing RPE region. Here, we suggest that Otx2 prevents the presumptive RPE region from forming the NR by repressing the expression of both Fgf8 and Sox2 which induce the NR cell fate.
authors.affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishihara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tabata
authors.forename: Masato
authors.initials: M
authors.lastname: Nakai
authors.forename: Nagaharu
authors.initials: N
authors.lastname: Tsukiji
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Katahira
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeda
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
authors.forename: Harukazu
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D030161:Avian Proteins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002642:Chick Embryo; D005123:Eye / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051857:Otx Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013687:Telencephalon / Q000196:embryology; D014162:Transfection
chemical_list: D030161:Avian Proteins; D051857:Otx Transcription Factors; D011993:Recombinant Fusion Proteins; D055748:SOXB1 Transcription Factors; D005346:Fibroblast Growth Factors