TY - JOUR
T1 - 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)
AU - Ohtsuka, Masato
AU - Kikuchi, Natsuko
AU - Yokoi, Hayato
AU - Kinoshita, Masato
AU - Wakamatsu, Yuko
AU - Ozato, Kenjiro
AU - Takeda, Hiroyuki
AU - Inoko, Hidetoshi
AU - Kimura, Minoru
N1 - Funding Information:
We thank Drs Hiroshi Hori, Daisuke Kobayashi and Masao Hyodo for providing the BAC library, bmp4 probe and hatching enzyme, respectively. We also thank Dr Atsuko Shimada for her help and advice in injection experiments. We are grateful to Dr Jochen Wittbrodt and members of his laboratory for technical advice in in situ hybridization and antibody staining. We thank Drs Kenji Imai, Lionel Larue, Rolf Kemler and Yasushi Taniguchi for valuable comments. We thank Dr Masafumi Tanaka for critical reading of the manuscript. This work was supported by Grant-in-Aid for Scientific Research (C) by the Ministry of Education, Science, Sports and Culture of Japan, and Research Fellowships of the Japan Society for the promotion of Science for Young Scientists to M.O.
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
KW - Dorsoventral
KW - Medaka
KW - Mirror-image
KW - Mutant
KW - Positional cloning
KW - Somite
KW - Spina bifida occulta
KW - Trunk-tail region
KW - zic
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U2 - 10.1016/j.mod.2004.04.006
DO - 10.1016/j.mod.2004.04.006
M3 - Article
C2 - 15210192
AN - SCOPUS:3042521352
VL - 121
SP - 873
EP - 882
JO - Cells and Development
JF - Cells and Development
SN - 2667-291X
IS - 7-8
ER -