Otx2 expression in anterior neuroectoderm and forebrain/midbrain is directed by more than six enhancers.
Otx2 plays essential roles in each site at each step of head development. We previously identified the AN1 enhancer at 91kb 5' upstream for the Otx2 expressions in anterior neuroectoderm (AN) at neural plate stage before E8.5, and the FM1 enhancer at 75kb 5' upstream and the FM2 enhancer at 122kb 3' downstream for the expression in forebrain/midbrain (FM) at brain vesicle stage after E8.5. The present study identified a second AN enhancer (AN2) at 88kb 5' upstream; the AN2 enhancer also recapitulates the endogenous Otx2 expression in choroid plexus, cortical hem and choroidal roof. However, the enhancer mutants indicated the presence of another AN enhancer. The study also identified a third FM enhancer (FM3) at 153kb 5' upstream. Thus, the Otx2 expressions in anterior neuroectoderm and forebrain/midbrain are regulated by more than six enhancers located far from the coding region. The enhancers identified are differentially conserved among vertebrates; none of the AN enhancers has activities in caudal forebrain and midbrain at brain vesicle stage after E8.5, nor do any of the FM enhancers in anterior neuroectoderm at neural plate stage before E8.5.
Laboratory for Vertebrate Body Plan, Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima Minami-machi, Chuo-Ku, Kobe, Hyogo 650-0047, Japan; Misaki Marine Biological Station, Graduate School of Science, The University of Tokyo, 1024 Koajiro, Misaki, Miura, Kanagawa 238-0225, Japan.
Daisuke
D
Kurokawa
Laboratory for Vertebrate Body Plan, Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima Minami-machi, Chuo-Ku, Kobe, Hyogo 650-0047, Japan.
Tomomi
T
Ohmura
Laboratory for Vertebrate Body Plan, Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima Minami-machi, Chuo-Ku, Kobe, Hyogo 650-0047, Japan.
Yusuke
Y
Sakurai
Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima Minami-machi, Chuo-Ku, Kobe, Hyogo 650-0047, Japan.
Kenichi
K
Inoue
Laboratory for Vertebrate Body Plan, Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima Minami-machi, Chuo-Ku, Kobe, Hyogo 650-0047, Japan.
Yoko
Y
Suda
Laboratory for Vertebrate Body Plan, Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima Minami-machi, Chuo-Ku, Kobe, Hyogo 650-0047, Japan; Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima Minami-machi, Chuo-Ku, Kobe, Hyogo 650-0047, Japan. Electronic address: saizawa@cdb.riken.jp.
Shinichi
S
Aizawa
D000818:Animals; D001483:Base Sequence; D002831:Choroid Plexus / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism*; D051857:Otx Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics
D051857:Otx Transcription Factors; C497656:Otx1 protein, mouse; C497660:Otx2 protein, mouse
Anterior neuroectoderm; Enhancer; Forebrain; Midbrain; Otx2