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Originally published In Press as doi:10.1074/jbc.C100767200 on June 7, 2002

J. Biol. Chem., Vol. 277, Issue 31, 28065-28069, August 2, 2002
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Identification, Tissue Expression, and Functional Characterization of Otx3, a Novel Member of the Otx Family*

Yan ZhangDagger , Takashi MikiDagger §, Toshihiko Iwanaga, Yoko Koseki||, Masaaki OkunoDagger , Yasuhiro SunagaDagger , Nobuaki OzakiDagger , Hideki YanoDagger , Haruhiko Koseki||, and Susumu SeinoDagger **

From the Departments of Dagger  Cellular and Molecular Medicine and || Molecular Embryology, Graduate School of Medicine, and § Gene Research Center, Chiba University, Chiba 260-8670, Japan and the  Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan

Transcription factors containing a homeodomain play an important role in the organogenesis of vertebrates. We have isolated a novel homeodomain transcription factor, Otx3, which is structurally and functionally related to Otx1 and Otx2, transcription factors that are critical in brain morphogenesis. Mouse Otx3 is a protein composed of 376 amino acids. Otx3 mRNA was expressed in mouse embryos from 10.5 to 13.5 days postcoitum (dpc) and in adult cerebellum as assessed by Northern blotting. Whole-mount in situ hybridization of mouse embryos from 9.5 to 11.5 dpc revealed strong expression of Otx3 mRNA in the diencephalon, mesencephalon, metencephalon, myelencephalon, and developing eye, indicating an expression pattern largely overlapping but distinct from those of Otx1 and Otx2. In addition, Otx3 was shown by electrophoretic mobility shift assay to bind to the TAATCC motif, the consensus binding sequence for Otx1, Otx2, and Crx. Results of a transcription reporter assay suggest that Otx3 functions as a transcription repressor by binding to this motif. These results suggest that Otx3 is a novel member of the Otx family and may be involved in the development of the central nervous system.

* This work was supported by grants-in-aid for creative scientific research and for scientific research from the Ministry of Education, Culture, Sports, Science and Technology; by a scientific research grant from the Ministry of Health, Labor and Welfare, Japan; by grants from Novo Nordisk Pharma Ltd. and from Takeda Chemical Industries Ltd.; and by the Yamanouchi Foundation for Research on Metabolic Disorders.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AB037698 and AB037699.

** To whom correspondence should be addressed. Tel.: 81-43-226-2187; Fax: 81-43-221-7803; E-mail: seino@med.m.chiba-u.ac.jp.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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