title: Possible roles of zic1 and zic4, identified within the medaka Double anal fin (Da) locus, in dorsoventral patterning of the trunk-tail region (related to phenotypes of the Da mutant).
abstract: Double anal fin (Da) is a spontaneous medaka mutant that exhibits an unique ventralizing phenotype, a mirror-image duplication across the lateral midline in the dorsal trunk-tail region. In the mutant, early D-V specification appears normal but the altered phenotype becomes evident during late embryogenesis. In this study, we genetically specified the mutation to a 174-kb region harboring two zinc-finger type transcription factors, zic1 and zic4, and compared the genomic structures of this region between wild-type and Da mutant fish. No mutation was found in the coding regions of either gene of the mutant, while two fragments, 324 bp and 3-4 kb long, were found inserted downstream of zic1 and zic4, respectively. Probably as a result of this, the expression of both genes is lost in the derivatives of the dorsal (epaxial) somite and the region dorsal to the terminal axis bending. All these tissues are morphologically affected or become ventralized in the mutants. In contrast, the expression in the head region and dorsal spinal cord remained unchanged. Detailed characterization of Da phenotypes revealed a novel defect in the axial skeleton (spina bifida occulta) that was also found in zic1-deficient mice. Finally, zic1-morpholino injection partially phenocopied early Da phenotypes. These findings strongly suggest that zic1 and/or zic4 are required for dorsal identity in the trunk-tail region and that loss of their expression in the epaxial somite derivatives and tail region causes the Da phenotypes.
authors.affiliation: Division of Basic Molecular Science and Molecular Medicine, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. masato@is.icc.u-tokai.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kikuchi
authors.forename: Hayato
authors.initials: H
authors.lastname: Yokoi
authors.forename: Masato
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Wakamatsu
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ozato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.forename: Minoru
authors.initials: M
authors.lastname: Kimura
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D001842:Bone and Bones / Q000002:abnormalities; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D009990:Oryzias / Q000002:abnormalities / Q000196:embryology* / Q000235:genetics*; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C100431:Zic4 protein, mouse; C492121:zic1 protein, zebrafish