Identification, tissue expression, and functional characterization of Otx3, a novel member of the Otx family.
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.
Zhang
Yan
Y
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Miki
Takashi
T
Iwanaga
Toshihiko
T
Koseki
Yoko
Y
Okuno
Masaaki
M
Sunaga
Yasuhiro
Y
Ozaki
Nobuaki
N
Yano
Hideki
H
Koseki
Haruhiko
H
Seino
Susumu
S
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology; D002460:Cell Line; D016384:Consensus Sequence; D017931:DNA Primers; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D017403:In Situ Hybridization; D007515:Islets of Langerhans; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D005810:Multigene Family; D051857:Otx Transcription Factors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C465213:DMBX1 protein, human; D017931:DNA Primers; D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; D014157:Transcription Factors