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

Daisuke Nishihara, Ichiro Yajima, Hiromasa Tabata, Masato Nakai, Nagaharu Tsukiji, Tatsuya Katahira, Kazuhisa Takeda, Shigeki Shibahara, Harukazu Nakamura, Hiroaki Yamamoto

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Article numbere48879
JournalPLoS ONE
Volume7
Issue number11
DOIs
Publication statusPublished - 2012 Nov 8
Externally publishedYes

Fingerprint

Retinal Pigments
retina
epithelium
pigments
Specifications
eyes
optics
Otx Transcription Factors
Optics
embryo (animal)
chicks
Gene encoding
dominant genes
cells
cell differentiation
early development
transcription factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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. / Nishihara, Daisuke; Yajima, Ichiro; Tabata, Hiromasa; Nakai, Masato; Tsukiji, Nagaharu; Katahira, Tatsuya; Takeda, Kazuhisa; Shibahara, Shigeki; Nakamura, Harukazu; Yamamoto, Hiroaki.

In: PLoS ONE, Vol. 7, No. 11, e48879, 08.11.2012.

Research output: Contribution to journalArticle

Nishihara, Daisuke ; Yajima, Ichiro ; Tabata, Hiromasa ; Nakai, Masato ; Tsukiji, Nagaharu ; Katahira, Tatsuya ; Takeda, Kazuhisa ; Shibahara, Shigeki ; Nakamura, Harukazu ; Yamamoto, Hiroaki. / 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. In: PLoS ONE. 2012 ; Vol. 7, No. 11.
@article{2978bb4dd98647cc886f1aeef2358722,
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.",
author = "Daisuke Nishihara and Ichiro Yajima and Hiromasa Tabata and Masato Nakai and Nagaharu Tsukiji and Tatsuya Katahira and Kazuhisa Takeda and Shigeki Shibahara and Harukazu Nakamura and Hiroaki Yamamoto",
year = "2012",
month = "11",
day = "8",
doi = "10.1371/journal.pone.0048879",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - 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

AU - Nishihara, Daisuke

AU - Yajima, Ichiro

AU - Tabata, Hiromasa

AU - Nakai, Masato

AU - Tsukiji, Nagaharu

AU - Katahira, Tatsuya

AU - Takeda, Kazuhisa

AU - Shibahara, Shigeki

AU - Nakamura, Harukazu

AU - Yamamoto, Hiroaki

PY - 2012/11/8

Y1 - 2012/11/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84869063084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869063084&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0048879

DO - 10.1371/journal.pone.0048879

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e48879

ER -