title: Kheper, a novel ZFH/deltaEF1 family member, regulates the development of the neuroectoderm of zebrafish (Danio rerio).
abstract: Kheper is a novel member of the ZFH (zinc-finger and homeodomain protein)/deltaEF1 family in zebrafish. kheper transcripts are first detected in the epiblast of the dorsal blastoderm margin at the early gastrula stage and kheper is expressed in nearly all the neuroectoderm at later stages. kheper expression was expanded in noggin RNA-injected embryos and also in swirl mutant embryos and was reduced in bmp4 RNA-injected embryos and chordino mutant embryos, suggesting that kheper acts downstream of the neural inducers Noggin and Chordino. Overexpression of Kheper elicited ectopic expansion of the neuroectoderm-specific genes fkd3, hoxa-1, and eng3, and the ectopic expression of hoxa-1 was not inhibited by BMP4 overexpression. Kheper interacted with the transcriptional corepressors CtBP1 and CtBP2. Overexpression of a Kheper mutant lacking the homeodomain or of a VP16-Kheper fusion protein disturbed the development of the neuroectoderm and head structures. These data underscore the role of Kheper in the development of the neuroectoderm and indicate that Kheper acts as a transcriptional repressor.
authors.affiliation: Department of Pharmacology, Division of Molecular Oncology, Department of Oncology, Biomedical Research Center, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. omuraoka@med.niigata-u.ac.jp
authors.forename: O
authors.initials: O
authors.lastname: Muraoka
authors.forename: H
authors.initials: H
authors.lastname: Ichikawa
authors.forename: H
authors.initials: H
authors.lastname: Shi
authors.forename: S
authors.initials: S
authors.lastname: Okumura
authors.forename: E
authors.initials: E
authors.lastname: Taira
authors.forename: H
authors.initials: H
authors.lastname: Higuchi
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: M
authors.initials: M
authors.lastname: Hibi
authors.forename: N
authors.initials: N
authors.lastname: Miki
mesh_terms: D000429:Alcohol Oxidoreductases; D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004475:Ectoderm / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D008845:Microinjections; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C081010:zfh1 protein, Drosophila; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein