Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression

Hiroki Danno, Tatsuo Michiue, Keisuke Hitachi, Akira Yukita, Shoichi Ishiura, Makoto Asashima

研究成果: Article

72 引用 (Scopus)


The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located ≈2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation.

ジャーナルProceedings of the National Academy of Sciences of the United States of America
出版物ステータスPublished - 08-04-2008


All Science Journal Classification (ASJC) codes

  • General