Updated on 2024/03/29

写真a

 
MAENO Mitsugu
 
Organization
Academic Assembly Institute of Science and Technology CHIKYU SEIBUTSU KAGAKU KEIRETU Professor
Graduate School of Science and Technology Life and Food Sciences Life Sciences Professor
Faculty of Science Department of Science Professor
Title
Professor
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Degree

  • 理学博士 ( 1987.12   北海道大学 )

Research Interests

  • Developmental Biology

  • 発生生物学

Research Areas

  • Life Science / Developmental biology

Research History (researchmap)

  • Niigata University   Graduate School of Science and Technology   Professor

    2012

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  • Niigata University   Faculty of Science   Associate Professor

    2007 - 2012

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  • Associate Prof, Niigata University, Faculty

    1994

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  • Niigata University   Faculty of Science   Associate Professor (as old post name)

    1994 - 2007

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  • 米国立がん研究所   フレデリックリサーチセンター   研究員

    1990 - 1994

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  • Visiting fellow, NIH, USA

    1990 - 1994

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  • Nihon University   School of Medicine   Research Assistant

    1986 - 1990

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  • Assistante prof., Nihon Univesity, School of

    1986 - 1990

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  • Med.

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  • of Sc.

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Research History

  • Niigata University   Faculty of Science Department of Biology   Professor

    2012.4

  • Niigata University   Graduate School of Science and Technology Life and Food Sciences Life Sciences   Professor

    2012.4

  • Niigata University   Faculty of Science Department of Biology   Associate Professor

    2004.4 - 2012.3

Education

  • Hokkaido University   理学研究科博士課程   動物学

    1984 - 1986

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  • Hokkaido University   Graduate School, Division of Natural Science

    - 1984

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  • Hokkaido University   理学研究科修士課程   動物学

    1982 - 1984

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    Country: Japan

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  • Hokkaido University   Faculty of Science   Department of Zoology

    - 1982

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  • Hokkaido University   School of Science   生物学科

    1977 - 1982

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    Country: Japan

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Professional Memberships

 

Papers

  • A <i>myeloperoxidase</i> enhancer drives myeloid cell‐specific labeling in a transgenic frog line

    Shiori Yamada‐Kondo, Ayame Ogawa, Miku Fukunaga, Yumi Izutsu, Takashi Kato, Mitsugu Maéno

    Development, Growth &amp; Differentiation   64 ( 7 )   362 - 367   2022.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    We have identified a myeloid cell-specific enhancer in the 5' flanking region of the Xenopus tropicalis myeloperoxidase gene. Transgenic reporter analysis using Xenopus laevis revealed that the expression of GFP was detected in the tail fin macrophages of a swimming tadpole, and the distributions of the GFP-positive and XL-2 (a pan-marker for leukocytes)-positive cells were mostly overlapping. The GFP-positive cells in the liver of the transgenic tadpole were localized in the same areas where the myeloid cells were present. Isolation of leukocytes from the peripheral blood cells followed by flow cytometric analysis revealed that the GFP-positive fraction was specifically enriched in neutrophils with lobulated nuclei. Furthermore, the macrophages purified from the peritoneal cavity were also GFP-positive. In summary, a transgenic frog line in which the myeloid cells are labeled with GFP provides a useful tool to elucidate the physiological role of myeloid cells of multiple origins in the embryo.

    DOI: 10.1111/dgd.12803

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/dgd.12803

  • Specific activation of the hb4 gene in the Xenopus oocyte through a Nobox-binding element located at the proximal promoter sequence. Reviewed

    Nakamigawa M, Kondo T, Maéno M

    Zygote   27 ( 4 )   195 - 202   2019.6

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  • Multiple origins of embryonic and tadpole myeloid cells in Xenopus laevis Reviewed

    Yasutaka Imai, Keisuke Ishida, Maya Nemoto, Keisuke Nakata, Takashi Kato, Mitsugu Maeno

    CELL AND TISSUE RESEARCH   369 ( 2 )   341 - 352   2017.8

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    Rabbit anti-serum against a myeloid-cell-specific peroxidase (Mpo) of Xenopus laevis was generated to identify myeloid cells in adult and larval animals. Smears of blood samples from adult hematopoietic organs were co-stained with Mpo and with XL-2, a mouse monoclonal antibody against a leukocyte common antigen. Lymphocytes found in the thymus and spleen were XL-2(+)Mpo(-) and granulocytes found in peripheral blood cells and the spleen were XL-2(+)Mpo(+), indicating that double-staining with these two antibodies allowed classification of the leukocyte lineages. Immunohistochemical analysis of larval organs showed that XL-2(+)Mpo(-) cells were scattered throughout the liver, whereas XL-2(+)Mpo(+) cells were present mainly in the cortex region. Interestingly, a cluster of XL-2(+)Mpo(+) cells was found in the region of the larval mesonephric rudiment. The ratio of XL-2(+)Mpo(+) cells to XL-2(+) cells in the mesonephric region was approximately 80%, which was much higher than that found in other hematopoietic organs. In order to elucidate the embryonic origin of the myeloid cells in the tadpole mesonephros, grafting experiments between X. laevis and X. borealis embryos were performed to trace the X. borealis cells as donor cells. Among the embryonic tissues examined, the tailbud tissue at the early neurula stage contributed greatly to the myeloid cluster in the mesonephric region at stage 48. Therefore, at least four independent origins of the myeloid cell population can be traced in the Xenopus embryo.

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  • Nkx2.5 is involved in myeloid cell differentiation at anterior ventral blood islands in the Xenopus embryo Reviewed

    Hiroyuki Sakata, Mitsugu Maeno

    DEVELOPMENT GROWTH & DIFFERENTIATION   56 ( 8 )   544 - 554   2014.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    We have shown previously that two populations of myeloid cells emerge in the anterior and posterior ventral blood islands (aVBI and pVBI) at the different stages in Xenopus laevis embryo. In order to elucidate the regulatory mechanism of myeloid cell differentiation in the aVBI, we examined the role of Nkx2.5, an essential transcription factor for heart differentiation, in regulation of the myeloid cell differentiation in this region. Knockdown of endogenous Nkx2.5 by introducing MO into the dorsal marginal zone (DMZ) suppressed the expression of MHC as well as that of mpo and spib in the resultant embryos and in DMZ explants made from the injected embryos. Expression of c/ebp was less affected in the embryos injected with Nkx2.5 MO. The effect of Nkx2.5 MO in myeloid cell differentiation was recovered by coinjection of nkx2.5 or c/ebp mRNA, indicating that Nkx2.5 functions at the same or the upper level of C/EBP for the specification of myeloid cells. An attempt to identify transcription factors for myeloid cell differentiation in ventral marginal zone (VMZ) explants demonstrated that coinjection of two transcription factors out of three factors, namely C/EBP, Nkx2.5 and GATA4, was sufficient to induce a certain amount of mpo expression. We suggest that C/EBP is an unequivocal factor for myeloid cell differentiation in the aVBI and that Nkx2.5 and GATA4 cooperate with C/EBP for promotion of myeloid cell differentiation.

    DOI: 10.1111/dgd.12155

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  • Expression and localization of Rdd proteins in Xenopus embryo Reviewed

    Jong-Chan Lim, Sayaka Kurihara, Rie Tamaki, Yutaka Mashima, Mitsugu Maéno

    Anatomy and Cell Biology   47 ( 1 )   18 - 27   2014

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Korean Association of Anatomists  

    The previous study has shown that repeated D domain-like (Rdd) proteins, a group of novel secretory proteinsconsisting of repeated domains of a cysteine-rich sequence, are involved in the process of blood vessel formation in Xenopusembryo. We performed further experiments to examine the localization of Rdd proteins in embryogenesis. Detection of taggedRdd proteins expressed in blastomeres showed that Rdd proteins formed a high molecular weight complex and existed in theextracellular space. A rabbit antibody against the Rdd synthetic peptide identified a single band of 28 kD in embryonic tissueextract. By whole-mount immunostaining analysis, signal was detected in the regions of inter-somites, vitelline veins, andbranchial arches at the tailbud stage. Staining of Rdd was remarkably reduced in the embryos injected with vascular endothelialgrowth factor Morpholino. We suggest that Rdd proteins interact with a molecule(s) associated with vascular precursor cells.

    DOI: 10.5115/acb.2014.47.1.18

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  • Distinct mechanisms control the timing of differentiation of two myeloid populations in Xenopus ventral blood islands Reviewed

    Mitsugu Maeno, Kyogo Komiyama, Yoko Matsuzaki, Junichi Hosoya, Sayaka Kurihara, Hiroyuki Sakata, Yumi Izutsu

    DEVELOPMENT GROWTH & DIFFERENTIATION   54 ( 2 )   187 - 201   2012.2

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    Previous study has suggested that distinct populations of myeloid cells exist in the anterior ventral blood islands (aVBI) and posterior ventral blood islands (pVBI) in Xenopus neurula embryo. However, details for differentiation programs of these two populations have not been elucidated. In the present study, we examined the role of Wnt, vascular endothelial growth factor (VEGF) and fibroblast growth factor signals in the regulation of myeloid cell differentiation in the dorsal marginal zone and ventral marginal zone explants that are the sources of myeloid cells in the aVBI and pVBI. We found that regulation of Wnt activity is essential for the differentiation of myeloid cells in the aVBI but is not required for the differentiation of myeloid cells in the pVBI. Endogenous activity of the VEGF signal is necessary for differentiation of myeloid cells in the pVBI but is not involved in the differentiation of myeloid cells in the aVBI. Overall results reveal that distinct mechanisms are involved in the myeloid, erythroid and endothelial cell differentiation in the aVBI and pVBI.

    DOI: 10.1111/j.1440-169X.2011.01321.x

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  • A novel approach for a toxicity prediction model of environmental pollutants by using a quantitative structure-activity relationship method based on toxicogenomics. Reviewed

    Hosoya J, Tamura K, Muraki N, Okumura H, Ito T, Maeno M

    ISRN toxicology   2011   515724   2011

  • Involvement of Neptune in induction of the hatching gland and neural crest in the Xenopus embryo Reviewed

    Takayuki Kurauchi, Yumi Izutsu, Mitsugu Maeno

    DIFFERENTIATION   79 ( 4-5 )   251 - 259   2010.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCI LTD  

    Neptune, a Kruppel-like transcription factor, is expressed in various regions of the developing Xenopus embryo and it has multiple functions in the process of development in various organs. In situ hybridization analysis showed that Neptune is expressed in the boundary region between neural and non-neural tissues at the neurula stage, but little is known about the function of Neptune in this region. Here, we examined the expression and function of Neptune in the neural plate border (NPB) in the Xenopus embryo. Depletion of Neptune protein in developing embryos by using antisense MO caused loss of the hatching gland and otic vesicle as well as malformation of neural crest-derived cranial cartilages and melanocytes. Neptune MO also suppressed the expression of hatching gland and neural crest markers such as he, snail2, sox9 and msx1 at the neurula stage. Subsequent experiments showed that Neptune is necessary and sufficient for the differentiation of hatching gland cells and that it is located downstream of pax3 in the signal regulating the differentiation of these cells. Thus, Neptune is a new member of hatching gland specifier and plays a physiological role in determination and specification of multiple lineages derived from the NPB region. (c) 2010 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.diff.2010.01.003

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  • Identification and expression of ventrally associated leucine-zipper (VAL) in Xenopus embryo Reviewed

    Yuko Saito, Yuhta Takahashi, Yumi Izutsu, Mitsugu Maeno

    INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY   54 ( 1 )   203 - 208   2010

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:U B C PRESS  

    In the present study, we have isolated a novel gene that is specifically expressed in the ventral region of Xenopus neurula and tailbud embryos. This gene, referred to as ventrally associated leucine-zipper (val), encodes for a novel class of protein consisting of a leucin-zipper motif, a glutamic acid-rich sequence and 5 repeats of proline-rich sequence. Expression of val started at the mid-gastrula stage, peaked at the early tailbud stage, and disappeared by the end of tailbud stage, and the endogenous expression of val was strictly dependent on BMP signaling. Myc-tagged val protein injected at early stage was accumulated in the nucleus at the gastrula stage and later, suggesting involvement of val in the process of ventral tissue formation during the neurula and tailbud stages.

    DOI: 10.1387/ijdb.082743ys

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  • The keratin-related Ouroboros proteins function as immune antigens mediating tail regression in Xenopus metamorphosis Reviewed

    Katsuki Mukaigasa, Akira Hanasaki, Mitsugu Maeno, Hiroshi Fujii, Shin-ichiro Hayashida, Mari Itoh, Makoto Kobayashi, Shin Tochinai, Masayuki Hatta, Kazuya Iwabuchi, Masanori Taira, Kazunori Onoe, Yumi Izutsu

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   106 ( 43 )   18309 - 18314   2009.10

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    Tail resorption during amphibian metamorphosis has been thought to be controlled mainly by a cell-autonomous mechanism of programmed cell death triggered by thyroid hormone. However, we have proposed a role for the immune response in metamorphosis, based on the finding that syngeneic grafts of tadpole tail skin into adult Xenopus animals are rejected by T cells. To test this, we identified two tail antigen genes called ouro1 and ouro2 that encode keratin-related proteins. Recombinant Ouro1 and Ouro2 proteins generated proliferative responses in vitro in T cells isolated from naive adult Xenopus animals. These genes were expressed specifically in the tail skin at the climax of metamorphosis. Overexpression of ouro1 and ouro2 induced T-cell accumulation and precocious tail degeneration after full differentiation of adult-type T cells when overexpressed in the tail region. When the expression of ouro1 and ouro2 were knocked down, tail skin tissue remained even after metamorphosis was complete. Our findings indicate that Ouro proteins participate in the process of tail regression as immune antigens and highlight the possibility that the acquired immune system contributes not only to self-defense but also to remodeling processes in vertebrate morphogenesis.

    DOI: 10.1073/pnas.0708837106

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  • Involvement of AP-2rep in morphogenesis of the axial mesoderm in Xenopus embryo Reviewed

    Yoshinari Saito, Masanori Gotoh, Yasutaka Ujiie, Yumi Izutsu, Mitsugu Maeno

    CELL AND TISSUE RESEARCH   335 ( 2 )   357 - 369   2009.2

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    We have previously isolated a cDNA clone coding for Xenopus AP-2rep (activator protein-2 repressor), a member of the Kruppel-like factor family, and reported its expression pattern in developing Xenopus embryos. In the present study, the physiological function of AP-2rep in the morphogenetic movements of the dorsal mesoderm and ectoderm was investigated. Embryos injected with either AP-2rep or VP16repC (a dominant-negative mutant) into the dorsal marginal zone at the 4-cell stage exhibited abnormal morphology in dorsal structures. Both AP-2rep and VP16repC also inhibited the elongation of animal cap explants treated with activin without affecting the expression of differentiation markers. Whole-mount in situ hybridization analysis revealed that expression of brachyury and Wnt11 was greatly suppressed by injection of VP16repC or AP-2rep morpholino, but expression was restored by the simultaneous injection of wild-type AP-2rep RNA. Furthermore, the morphogenetic abnormality induced by injection of VP16repC or AP-2rep morpholino was restored by simultaneous injection of brachyury or Wnt11 mRNA. These results show that AP-2rep is involved in the morphogenesis of the mesoderm at the gastrula stage, via the brachyury and/or Wnt pathways.

    DOI: 10.1007/s00441-008-0712-7

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  • A role of D domain-related proteins in differentiation and migration of embryonic cells in Xenopus laevis Reviewed

    Tomoko Shibata, Yuhta Takahashi, Junichi Tasaki, Yuko Saito, Yumi Izutsu, Mitsugu Maeno

    MECHANISMS OF DEVELOPMENT   125 ( 3-4 )   284 - 298   2008.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    We have characterized a cDNA clone, rdd (repeated D domain-like), that encodes for a secretory protein consisting of repeated domains of cysteine-rich sequence. Whole-mount in situ hybridization analysis revealed that rdd2, rdd3 and rdd4 are transiently expressed in the ventral and lateral mesoderm and the overlying ectoderm at the late gastrula and tailbud stages. Morpholino oligonucleotide (MO) was used to inhibit the translation of endogenous rdd3 and rdd4, and we found that the circulation of red blood cells completely disappears in the MO-injected tadpoles. Histological analysis showed that formation of the ventral aorta, dorsal aorta and posterior cardinal vein in the trunk region was severely disorganized in these animals. injection of MO affected the expression of alpha-globin, a terminal differentiation marker of red blood cells, but did not affect the expression of scl, flk-1 or tie-2, suggesting that angiopoietic and hematopoietic precursor cells differentiate normally in the rdd-depleted embryo. The transplantation of labeled tissues followed by tracing of the donor cells revealed a role of rdds in migration of the embryonic angioblasts and myeloid cells. These observations first demonstrate the role of the novel cysteine-rich proteins in migration of the embryonic cells. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.mod.2007.11.003

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  • Nuclear envelope precursor vesicle targeting to chromatin is stimulated by protein phosphatase 1 in Xenopus egg extracts Reviewed

    Hiromi Ito, Yuhei Koyama, Makoto Takano, Kohei Ishii, Mitsugu Maeno, Kazuhiro Furukawa, Tsuneyoshi Horigome

    EXPERIMENTAL CELL RESEARCH   313 ( 9 )   1897 - 1910   2007.5

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    The mechanism underlying targeting of the nuclear membrane to chromatin at the end of mitosis was studied using an in vitro cell-free system comprising Xenopus egg membrane and cytosol fractions, and sperm chromatin. The mitotic phase membrane, which was separated from a mitotic phase extract of Xenopus eggs and could not bind to chromatin, became able to bind to chromatin on pretreatment with a synthetic phase cytosol fraction of Xenopus eggs. When the cytosol fraction was depleted of protein phosphatase 1 (PP1) with anti-Xenopus PP1-gamma 1 antibodies, this ability was lost. The addition of recombinant xPP1 gamma 1 to the PP1-depleted cytosol fraction restored the ability. These and other results suggested that dephosphorylation of mitotic phosphorylation sites on membranes by PP1 in the synthetic phase cytosol fraction promoted targeting of the membranes to chromatin. On the other hand, a fragment containing the chromatin-binding domain of lamin B receptor (LBR) but not emerin inhibited targeting of membrane vesicles. It was also shown that PP1 dephosphorylates a phosphate group(s) responsible for regulation of the binding of LBR to chromatin. A possible mechanism involving PP1 and LBR for the regulation of nuclear membrane targeting to chromatin was discussed. (c) 2007 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.yexcr.2007.03.015

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  • Characterization of myeloid cells derived from the anterior ventral mesoderm in the Xenopus laevis embryo Reviewed

    Sumihisa Tashiro, Ayako Sedohara, Makoto Asashima, Yumi Izutsu, Mitsugu Maeno

    DEVELOPMENT GROWTH & DIFFERENTIATION   48 ( 8 )   499 - 512   2006.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BLACKWELL PUBLISHING  

    A recent study revealed the presence of a unique population of myeloid cells in the anterior ventral (AV) mesoderm of Xenopus laevis embryo, as characterized by the expression of peroxidase 2 (POX2), which encodes for a leukocyte-specific enzyme. The current report further characterized the POX2-positive cells in terms of their contribution to hematopoiesis in tadpole and regulatory mechanism in differentiation. Grafting experiments with cytogenetically labeled tissues revealed that AV-derived mesoderm supplies a transient population of migrating leukocytes in the mesenchyme of early tadpole. These cells were rarely found in blood vessels at any stages. Using a ventral marginal zone explant system, we demonstrated that dkk1, shown as a heart inducer in this system, has a strong ability to induce the expression of POX2. Injection of a high dose dkk1 RNA induced a heart marker while a low dose of dkk1 preferentially induced the expression of POX2, suggesting that dkk1 works as a morphogen to determine the different lineages. Overall results indicate that wnt signal inhibitors induce leukocytes at the early neurula stage and that these cells spread to the entire body and exist until the ventral blood island-derived leukocytes appear in the body.

    DOI: 10.1111/j.1440-139x.2006.00885.x

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  • Neptune is involved in posterior axis and tail formation in Xenopus embryogenesis Reviewed

    M Takeda, T Kurauchi, T Yamazaki, Y Izutsu, M Maeno

    DEVELOPMENTAL DYNAMICS   234 ( 1 )   63 - 73   2005.9

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    In order to elucidate the molecular mechanisms underlying the posterior axis and tail formation in embryogenesis, the function of Neptune, a zinc-finger transcription factor, in Xenopus laevis embryos was investigated. Injection of neptune mRNA into the animal pole area of embryos resulted in the formation of an additional tail structure that included a neural tube and muscle tissue. This activity required FGF signaling since coinjection of a dominant-negative FGF receptor RNA (XFD) completely blocked the formation of a tail structure. A loss-of-function experiment using a fusion construct of neptune and Drosophila engrailed (en-neptune) RNA showed that endogenous Neptune is necessary for formation of the posterior trunk and tail. Furthermore, activity of Neptune was necessary for the endogenous expression of brachyury and fgf-8 at the late gastrula stage. These findings demonstrate a novel function of Neptune in the process of anterior-posterior axis formation through the FGF and brachyury signaling cascades. An experiment using a combination explant with ventral and dorsal marginal tissues showed that cooperation of these two distinct tissues is important for the tail formation and that expression of Neptune in prospective ventral cells may be involved in the activation of the process of tail formation. (c) 2005 Wiley-Liss, Inc.

    DOI: 10.1002/dvdy.20518

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  • Analyses of immune responses to ontogeny-specific antigens using an inbred strain of Xenopus laevis (J strain). Reviewed

    Izutsu Y, Maéno M

    Methods in molecular medicine   105   149 - 158   2005

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  • Xenopus laevis macrophage migration inhibitory factor is essential for axis formation and neural development Reviewed

    M Suzuki, Y Takamura, M Maeno, S Tochinai, D Iyaguchi, Tanaka, I, J Nishihira, T Ishibashi

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 20 )   21406 - 21414   2004.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine involved in both acquired and innate immunity. MIF also has many functions outside the immune system, such as isomerase and oxidoreductase activities and control of cell proliferation. Considering the involvement of MIF in various intra- and extracellular events, we expected that MIF might also be important in vertebrate development. To elucidate the possible role of MIF in developmental processes, we knocked down MIF in embryos of the African clawed frog Xenopus laevis, using MIF-specific morpholino oligomers (MOs). For the synthesis of the MOs, we cloned a cDNA for a Xenopus homolog of MIF. Sequence analysis, determination of the isomerase activity, and x-ray crystallographic analysis revealed that the protein encoded by the cDNA was the ortholog of mammalian MIF. We carried out whole mount in situ hybridization of MIF mRNA and found that MIF was expressed at high levels in the neural tissues of normal embryos. Although early embryogenesis of MO-injected embryos proceeded normally until the gastrula stage, their neurulation was completely inhibited. At the tailbud stage, the MO-injected embryos lacked neural and mesodermal tissues, and also showed severe defects in their head and tail structures. Thus, MIF was found to be essential for axis formation and neural development of Xenopus embryos.

    DOI: 10.1074/jbc.M311416200

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  • A BMP-4-dependent transcriptional control element in the 5 ' flanking region of Xenopus SCL gene Reviewed

    T Sanada, M Park, A Araki, M Gotoh, Y Izutsu, M Maeno

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   310 ( 4 )   1160 - 1167   2003.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We isolated 5.5 kb genomic DNA fragment of Xenopus stem cell leukemia (SCL) that contains approximately 1.5 kb of the 5' flanking region and 4.0 kb of the first intron between a non-coding exon (exon 1) and a coding exon (exon 2). Sequencing result of the 5' flanking region has shown that there is a portion that shares 85% and 69% with the sequences of avian and mammalian genomes of SCL promoter region (-64 to +73). The 1.5 kb 5' flanking region of SCL genome and various deletion constructs were inserted at the upstream of luciferase (luc) gene and used for the reporter assay. The reporter activity was first detected at the neurula stage in the embryos injected with -167 + 157llucc at the 2-cell stage and the values increased as the stages advanced. The experiments using dominant-negative constructs revealed that the activation of SCL transcription via the 5' flanking region requires the BMP-4 and GATA factors. Taken together with the in situ hybridization analysis indicating that expression of SCL was downregulated in the central nervous system in BMP-depleted embryos, the proximal sequence of SCL consists of a stage-dependent and BMP signaling-dependent control element. (C) 2003 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2003.09.135

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  • Regulatory signals and tissue interactions in the early hematopoietic cell differentiation in Xenopus laevis embryo Reviewed

    M Maeno

    ZOOLOGICAL SCIENCE   20 ( 8 )   939 - 946   2003.8

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    Bone morphogenetic protein-4 (BMP-4) has been shown as an essential factor in differentiation of the primitive blood cells in Xenopus laevis embryo. Organizer factors, in contrast, function as a negative regulator for the blood cell differentiation. Differentiation of both blood cells and muscle tissue are negatively regulated by the organizer activity. However, blood cells but not muscle tissue can differentiate in the organizer-depleted embryos produced by removal of vegetal cortex cytoplasm at the one-cell stage. Thus the blood cells are totally independent cells from the organizer activity. The down-stream target molecules of the BMP-4 signaling, such as vent-1/2 and msx-1/2 are the positive regulators for muscle tissue differentiation, whereas these factors do not promote blood cell formation. It has not yet been elucidated how the BMP-4 signaling promotes the differentiation of blood cells, but it is likely that transcription factors such as GATA-2, SCL, LMO-2, biklf and GATA-1 are at least involved in the initial blood program. Experiments using combined germ layer explants suggest that interaction between ectoderm and mesoderm at the gastrula stage is important for the blood cell formation in mesoderm. BMP-4 produced in the ectodermal cells is essential for this interaction. For understanding the whole program in the embryonic blood cell differentiation, it is important to elucidate the molecular mechanisms underlying the tissue-tissue interaction, in addition to the analysis of the regulatory cascade that takes place in the mesodermal cells.

    DOI: 10.2108/zsj.20.939

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  • Complementary expression of AP-2 and AP-2rep in ectodermal derivatives of Xenopus embryos Reviewed

    M Gotoh, Y Izutsu, M Maeno

    DEVELOPMENT GENES AND EVOLUTION   213 ( 7 )   363 - 367   2003.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER-VERLAG  

    In an attempt to define the pattern of developmental expression of AP-2rep and AP-2 in Xenopus embryos, we cloned a Xenopus AP-2rep cDNA. The AP-2rep message was localized in the organizer region at the gastrula stage whereas AP-2 was expressed ventrolaterally in the animal hemisphere. Later, AP-2rep was expressed in the entire neural tissue at the neurula stage while AP-2 was predominantly expressed in the cranial neural crest areas. The endogenous expression of AP-2 in the neural crest area was diminished by ectopic injection of AP-2rep RNA, suggesting a role for AP-2rep in the differentiation of neural tissues by restricting the expression of AP-2 in the Xenopus embryo.

    DOI: 10.1007/s00427-003-0336-6

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  • Ontogenic emergence and localization of larval skin antigen molecule recognized by adult T cells of Xenopus laevis: Regulation by thyroid hormone during metamorphosis Reviewed

    M Watanabe, M Ohshima, M Morohashi, M Maeno, Y Izutsu

    DEVELOPMENT GROWTH & DIFFERENTIATION   45 ( 1 )   77 - 84   2003.2

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    Results from previous studies using an inbred strain of Xenopus laevis have led to the proposition that metamorphosis includes the events by which the newly differentiating adult immune system, including T lymphocytes, recognizes and eliminates larval skin cells as 'non-self'. More recently, a larval antigen targeted by adult T cells was identified as a 59 kDa protein with a specific peptide sequence. Using antisera directed against the larval antigen and the peptide, immunohistochemistry and western blotting were done to examine expression of the 59 kDa larval antigen in the skin during larval and metamorphic periods. There was no expression before Nieuwkoop and Faber stage 53. Expression was first seen at the beginning of metamorphic stage 54, when hind limbs appear, and increased thereafter, in apical and skein cells of both trunk and tail regions. In the trunk region, expression started to decrease at stage 58, until it completely disappeared at stage 62 (metamorphic climax). In the tail skin, however, expression persisted throughout the metamorphic stages. Treatment of larvae with thyroid hormone (TH) resulted in repression of expression of the 59 kDa molecule in a dose-dependent manner. Downregulation occurred earlier in the trunk than in the tail skin. These results suggest involvement in metamorphic events of an immunological mechanism: differential expression of the larval antigen in the trunk and tail skin cells due to their differing concentration of TH results in the tail, but not the trunk skin, being selectively attacked by the newly differentiating adult-type immune system.

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  • Larval antigen molecules recognized by adult immune cells of inbred Xenopus laevis: Partial characterization and implication in metamorphosis Reviewed

    Y Izutsu, S Tochinai, M Maeno, K Iwabuchi, K Onoe

    DEVELOPMENT GROWTH & DIFFERENTIATION   44 ( 6 )   477 - 488   2002.12

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    It has been shown that larval skin (LS) grafts are rejected by an inbred strain of adult Xenopus, which suggests a mechanism of metamorphosis by which larval cells are recognized and attacked by the newly differentiating immune system, including T lymphocytes. In an attempt to define the larval antigenic molecules that are targeted by the adult immune system, anti-LS antibodies (IgY) were produced by immunizing adult frogs with syngeneic LS grafts. The antigen molecules that reacted specifically with this anti-LS antiserum were localized only in the larval epidermal cells. Of 53 and 59-60 kDa acidic proteins that were reactive with anti-LS antibodies, a protein of 59 kDa and with an isoelectric point of 4.5 was selected for determination of a 19 amino acid sequence (larval peptide). The rat antiserum raised against this peptide was specifically reactive with the 59 kDa molecules of LS lysates. Immunofluorescence studies using these antisera revealed that the larval-specific molecules were localized in both the tail and trunk epidermis of premetamorphic larvae, but were reduced in the trunk regions during metamorphosis, and at the climax stage of metamorphosis were detected only in the regressing tail epidermis. Culture of splenocytes from LS-immunized adult frogs in the presence of larval peptide induced augmented proliferative responses. Cultures of larval tail pieces in T cell-enriched splenocytes from normal frogs or in natural killer (NK)-cell-enriched splenocytes from early thymectomized frogs both resulted in significant destruction of tail pieces. Tissue destruction in the latter was enhanced when anti-LS antiserum was added to the culture. These results indicate that degeneration of tail tissues during metamorphosis is induced by a mechanism such that the larval-specific antigen molecules expressed in the tail epidermis are recognized as foreign by the newly developing adult immune system, and destroyed by cytotoxic T lymphocytes and/or NK cells.

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  • Common and distinct signals specify the distribution of blood and vascular cell lineages in Xenopus laevis embryos Reviewed

    F Iraha, Y Saito, K Yoshida, M Kawakami, Y Izutsu, IO Daar, M Maeno

    DEVELOPMENT GROWTH & DIFFERENTIATION   44 ( 5 )   395 - 407   2002.10

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    In an effort to elucidate the regulatory mechanisms that determine the fate of blood cells and vascular cells in the ventral blood island mesoderm, the embryonic expression of Xtie-2, a Xenopus homolog of the tie-2 receptor tyrosine kinase, was examined. Whole-mount in situ hybridization analysis revealed that Xtie-2 mRNA is expressed at the late tailbud stage within the regions where endothelial precursor cells exist. On the ventral side of embryos, Xtie-2-positive cells are predominantly present just outside the boundary of alpha-globin-positive cells, thus the expression pattern of these two markers seems mutually exclusive. Further experiments revealed that there is a consistent and strong correlation between the induction of Xtie-2 and alpha-globin expression in embryos and explant tissues. First, these two markers displayed overlapping expression in embryos ventralized by the removal of a 'dorsal determinant' from the vegetal cytoplasm at the 1-cell stage. Second, expression of both Xtie-2 and alpha-globin were markedly induced in ectodermal explants (animal caps) from embryos co-injected with activin and bone morphogenetic protein (BMP)-4 RNA. Furthermore, both Xtie-2 and alpha-globin messages were strongly positive in dorsal marginal zone explants that had been injected with BMP-4 RNA. In contrast, however, there was a clear distinction in the localization of these two transcripts in embryos dorsalized by LiCl treatment. Distinct localization was also found in the ventral marginal zone (VMZ) explants. Using the VMZ explant system, we demonstrate a role of fibroblast growth factor (FGF) signaling in enhancing the vascular cell marker and reducing the blood cell marker. The present study suggests that the early steps of blood and vascular cell differentiation are regulated by a common BMP-4-dependent signaling; however, distinct factor(s) such as FGF are involved in different distribution of these two cell lineages.

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  • Two-step induction of primitive erythrocytes in Xenopus laevis embryos: signals from the vegetal endoderm and the overlying ectoderm Reviewed

    M Kikkawa, M Yamazaki, Y Izutsu, M Maeno

    INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY   45 ( 2 )   387 - 396   2001.4

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    Primitive blood cells differentiate from the ventral mesoderm blood islands in Xenopus embryos. In order to determine the tissue interactions that propagate blood formation in early embryogenesis, we used embryos that had the ventral cytoplasm removed. These embryos gastrulated normally, formed a mesodermal layer and lacked axial structures, but displayed a marked enhancement of alpha -globin expression. Early ventral markers, such as msx-1, vent-1 and vent-2 were highly expressed at the gastrula stage, while a dorsal marker, goosecoid, was diminished. Several lines of experimental evidence demonstrate the critical role of animal pole-derived ectoderm in blood cell formation: 1) Mesoderm derived from dorsal blastomeres injected with beta -galactosidase mRNA las a lineage tracer) expressed alpha -globin when interfaced with an animal pole-derived ectodermal layer; 2) Embryos in which the animal pole tissue had been removed by dissection at the blastula stage failed to express alpha -globin; 3) Exogastrulated embryos that lacked an interaction between the mesodermal and ectodermal layers failed to form blood cells, while muscle cells were observed in these embryos. Using dominant-negative forms of the BMP-4 and ALK-4 receptors, we showed that activin and BMP-4 signaling is necessary for blood cell differentiation in ventral marginal zone explants, while FGF signaling is not essential. In ventralized embryos, inactivation of the BMP-4 signal within a localized area of the ectoderm led to suppression of globin expression in the adjacent mesoderm layer, but inactivation of the activin signal did not have th is effect. These observations suggest that mesodermal cells, derived from a default pathway that is induced by the activin signal, need an additional BMP-4-dependent factor from the overlying ectoderm for further differentiation into a blood cell lineage.

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  • Expression and function of Xmsx-2B in dorso-ventral axis formation in gastrula embryos Reviewed

    Onitsuka, I, M Takeda, M Maeno

    ZOOLOGICAL SCIENCE   17 ( 8 )   1107 - 1113   2000.11

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    Msx is a homeodomain-containing transcriptional factor that plays an essential role in pattern formation in vertebrata and invertebrata embryos. In Xenopus laevis, two msx genes have been identified (Xmsx-1 and Xmsx-2). In the present study, we attempted to elucidate the expression and function of Xmsx-2B (formerly designated as Xhox7.1') in early embryogenesis. Whole mount in situ hybridization analyses showed that the expression pattern of Xmsx-2B at gastrula and neurula stages was very similar to that of Xmsx-1: the transcript of Xmsx-2B was observed in ventral and lateral sides of the embryo. At the tailbud stage, however, the expression pattern of Xmsx-2B in neural tissues was distinct from that of Xmsx-1. An RNA injection experiment revealed that, like BMP-4, Xmsx-2B has a strong ventralizing activity. In the Xmsx-2B-injected embryos, differentiation of axial structures such as the notochord, muscle, and neural tissue was completely suppressed, whereas alpha -globin mRNA, a blood cell marker, was highly expressed. Simultaneous injection of Xmsx-1 and Xmsx-2B RNAs showed that they function in an additive manner. It was also shown that coinjection of Xmsx-2B with a dominant-negative BMP-4 receptor (tBR), which can induce formation of secondary axis when injected alone in ventral blastomeres, suppressed secondary axis formation. Furthermore, Xmsx-2B also suppressed secondary axis formation, which was induced by a dominant-negative form of Xmsx-1 (VP16/msx-1). Therefore, like Xmsx-1, Xmsx-2B is a downstream nuclear factor of the BMP-4-derived ventralizing signal, and these two factors probably share the same target molecules. In conclusion, Xmsx-1 and Xmsx-2B function in dorso-ventral axis formation in early Xenopus laevis development.

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  • Involvement of BMP-4/msx-1 and FGF pathways in neural induction in the Xenopus embryo Reviewed

    A Ishimura, R Maeda, M Takeda, M Kikkawa, IO Daar, M Maeno

    DEVELOPMENT GROWTH & DIFFERENTIATION   42 ( 4 )   307 - 316   2000.8

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    The msx homeodomain protein is a downstream transcription factor of the bone morphogenetic protein (BMP)-4 signal and a key regulator for neural tissue differentiation. Xmsx-1 antagonizes the dorsal expression of noggin and cerberus, as revealed by in situ hybridization and reverse transcription-polymerase chain reaction assays. In animal cap explants, Xmsx-1 and BMP-4 inhibit the neural tissue differentiation induced by noggin or cerberus. A loss-of-function study using the Xmsx-1/VP-16 fusion construct indicated that neural tissue formation was directly induced by the injection of fusion ribonucleic acid, although the expression of neural cell adhesion molecule (N-CAM) in the cap was less than that in the cap injected with tBR or noggin. In contrast to the single cap assay, unexpectedly, both BMP-4 and Xmsx-1 failed to inhibit neurulation in the ectodermal explants to which the organizer mesoderm was attached. The results of cell-lineage tracing experiments indicated that the neural cells were differentiated from the animal pole tissue where the excess RNA of either BMP-4 or Xmsx-1 was injected, whereas notochord was differentiated from the organizer mesoderm. Neural tissue differentiated from BMP-4-injected ectodermal cells strongly expressed posterior neural markers, such as hoxB9 and krox20, suggesting that the posterior neural cells differentiated regardless of the existence of the BMP signal. The introduction of a dominant-negative form of the fibroblast growth factor (FGF) receptor (XFD) into the ectodermal cells drastically reduced the expression of pan and posterior neural markers (N-CAM and hoxB-9) if co-injected with BMP-4 RNA, although XFD alone at the same dose did not shut down the expression of N-CAM in the combination explants. Therefore, it is proposed that an FGF-related molecule was involved in the direct induction of posterior neural tissue in the inducing signals from the organizer mesoderm in vivo.

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  • Xenopus msx-1 regulates dorso-ventral axis formation by suppressing the expression of organizer genes. Reviewed

    Takeda M, Saito Y, Sekine R, Onitsuka I, Maeda R, Maéno M

    Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology   126 ( 2 )   157 - 168   2000.6

  • Immunodetection of Xenopus bone morphogenetic protein-1 in adult and embryonic cells Reviewed

    A Ishimura, GL Princler, JJ Lin, HF Kung, M Maeno

    GROWTH FACTORS   16 ( 3 )   171 - 177   1999

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    In order to analyze biochemical properties of Xenopus bone morphogenetic protein-1 (XBMP-1), rabbit antiserum (alpha-B1) was raised against a synthetic peptide (P1) corresponding to a hydrophilic N-terminal region. XBMP-1B (Xtld) synthesized in the reticulocyte lysate was successfully immunoprecipitated by this antiserum. This precipitation was completely blocked when Pi was added to the reaction, indicating that alpha-B1 recognized XBMP-1B specifically. In Western blot analysis, two distinct sizes of protein (107 and 34 kD) were detected in hind limbs in metamorphosing animals. Both proteins were detected in various adult tissues such as lung, liver, kidney, heart, muscle, intestine, brain, and testis, The mixing of the liver and muscle extracts, and the following detection of immunoreactive proteins suggested that the 34 kD band was a proteolytic product of the 107 kD protein. In the embryonic extracts from the unfertilized egg (stage 0) to swimming tadpoles (stage 40), a 63 kD protein was detected in addition to the 107 kD protein. We also showed that the 107 kD protein was much more expressed in the animal half of the unfertilized eggs than in the vegetal half, but that it was ubiquitously expressed in the gastrula embryos. We suggest that the 63 and 107 kD proteins correspond to full-length proteins encoded by XBMP-1A and XBMP-1B genes, and these proteins are expressed in embryo and in various adult tissues.

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  • GATA-1 inhibits the formation of notochord and neural tissue in Xenopus embryo Reviewed

    K Shibata, A Ishimura, M Maeno

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   252 ( 1 )   241 - 248   1998.11

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    The expression of GATA-1, which encodes for a hemopoietic transcription factor, initiates at gastrula stage in the Xenopus embryo (1). In order to examine a possible function of GATA-1 in dorso-ventral patterning of mesoderm and ectoderm derivatives, the synthesized RNA of GATA-1 was overexpressed in embryonic cells to assess its biological effects. In the embryos injected with GATA-1 RNA in the dorsal marginal zone at 4-cell stage, dorsal epidermis did not cover the vegetal cells so that the gastrulation was not completed. The same dose of GATA-1 RNA injected into ventral marginal zone did not influence the development, and GATA-2 RNA transcribed from the same vector had little effect, suggesting that this phenomenon is physiologically important. The morphological and immunohistochemical studies revealed that notochord and neural tissue were mostly eliminated in the embryos or the dorsal marginal zone explants after injection of GATA-1 RNA. GATA-1 also inhibited neurogenesis in animal cap explants, which was induced by the injection with noggin RNA. Northern blot analysis using dorsal marginal zone explants showed, however, that only a slight amount of alpha-globin message was induced, and cardiac alpha-actin message was retained. Therefore, GATA-1 did not convert completely the dorsal phenotype to the ventral one. Furthermore, the injection of GATA-1 RNA didnot alter the expression of early dorsal and ventral markers at the onset of gastrulation. These results suggest that GATA-1 is an potential inhibitor of the dorsalization and the neurogenesis, but it affects on the specification of dorsal tissues in relatively later steps. (C) 1998 Academic Press.

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  • Xmsx-1 modifies mesodermal tissue pattern along dorsoventral axis in Xenopus laevis embryo Reviewed

    R Maeda, A Kobayashi, R Sekine, JJ Lin, HF Kung, M Maeno

    DEVELOPMENT   124 ( 13 )   2553 - 2560   1997.7

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    This study analyzes the expression and the function of Xenopus msx-1 (Xmsx-1) in embryos, in relation to the ventralizing activity of bone morphogenetic protein-4 (BMP-4), Expression of Xmsx-1 was increased in UV-treated ventralized embryos and decreased in LiCl-treated dorsalized embryos at the neurula stage (stage 14). Whole-mount in situ hybridization analysis showed that Xmsx-1 is expressed in marginal zone and animal pole areas, laterally and ventrally, but not dorsally, at mid-gastrula (stage 11) and late-gastrula (stage 13) stages. Injection of BMP-4 RNA, but not activin RNA, induced Xmsx-1 expression in the dorsal marginal zone at the early gastrula stage (stage 10+), and introduction of a dominant negative form of BMP-4 receptor RNA suppressed Xmsx-1 expression in animal cap and ventral marginal zone explants at stage 14. Thus, Xmsx-1 is a target gene specifically regulated by BMP-4 signaling. Embryos injected with Xmsx-1 RNA in dorsal blastomeres at the 4-cell stage exhibited a ventralized phenotype, with microcephaly and swollen abdomen. Histological observation and immunostaining revealed that these embryos had a large block of muscle tissue in the dorsal mesodermal area instead of notochord. On the basis of molecular marker analysis, however, the injection of Xmsx-1 RNA did not induce the expression of alpha-globin, nor reduce cardiac alpha-actin in dorsal marginal zone explants. Furthermore, a significant amount of alpha-actin was induced and alpha-globin was turned off in the ventral marginal zone explants injected with Xmsx-1. These results indicated that Xmsx-1 is a target gene of BMP-4 signaling, but possesses a distinct activity on dorsal-ventral patterning of mesodermal tissues.

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  • XBMP-1B (Xtld), a Xenopus homolog of dorso-ventral polarity gene in Drosophila, modifies tissue phenotypes of ventral explants Reviewed

    JJ Lin, R Maeda, RC Ong, JB Kim, LM Lee, HF Kung, M Maeno

    DEVELOPMENT GROWTH & DIFFERENTIATION   39 ( 1 )   43 - 51   1997.2

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    Previously we have isolated a Xenopus cDNA homolog of bone morphogenetic protein-1 (XBMP-1A). In the present report we describe a new cDNA clone called XBMP-1B (or Xtld) from a Xenopus embryonic library. Sequence analysis indicates that these two clones share an identical N-terminal sequence, including a region of metalloprotease domain, three copies of a repeat first found in complement proteins C1r/s and an epidermal growth factor (EGF)-like sequence. XBMP-1B protein has an additional copy of an EGF-like sequence followed by two copies of complement 1 r/s repeat in the C-terminus. The overall protein structure predicted from the XBMP-1B sequence reveals that it encodes a protein homologous to Drosophila tolloid. Three XBMP-1 transcripts (2.9, 5.2 and 6.6 kb) were detected by northern blot analysis. However, the 2.9 kb transcript hybridized specifically with XBMP-1A and the 5.2 and 6.6 kb transcripts hybridized with XBMP-1B. In Drosophila, a major function of tolloid is to augment the activity of the decapentaplegic gene product, a close relative of tumor growth factor (TGF)-beta superfamily members, BMP-2/4. Although XBMP-1 and XBMP-4 are detected in various adult tissues of Xenopus, the expression pattern of these two genes was not tightly correlated. In the embryo, the expression of XBMP-1 increased gradually from the morula to the swimming tadpole stages. Injection of XBMP-1B RNA into the ventral blastomeres at the 4-cell stage caused an elongation of the ventral marginal zone explants and converted globin-positive blood cells to mesenchymal and muscle tissues at later stages. It was shown that XBMP-1A was less active and a 1A mutant lacking the signal sequence was inactive. Further studies revealed that injection of XBMP-1B RNA into the ventral marginal zone induced up-regulation of dorsal marginal zone markers, such as goosecoid and chordin, at the gastrulation stage. These data indicate that XBMP-1 may have a role in determining dorso-ventral patterning in Xenopus, but in a different way from the dpp/tolloid system demonstrated in Drosophila.

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  • The role of BMP-4 and GATA-2 in the induction and differentiation of hematopoietic mesoderm in Xenopus laevis Reviewed

    M Maeno, PE Mead, C Kelley, RH Xu, HF Kung, A Suzuki, N Ueno, LI Zon

    BLOOD   88 ( 6 )   1965 - 1972   1996.9

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    Vertebrate embryonic blood formation is regulated by factors that participate in dorsal-ventral patterning and mesoderm induction. The GATA-binding transcription factors are required for normal hematopoiesis and are expressed during gastrulation when ventral mesoderm (VM) is induced to form blood. Based on the recent demonstration that bone morphogenetic protein (BMP-4) is a potent ventralizing factor and inducer of hematopoietic tissue, we hypothesized that GATA-2 could be induced or activated by BMP-4. Here we demonstrate that BMP-4 can stimulate GATA-5 expression, and that expression of a dominant negative BMP-4 receptor can suppress GATA-2 induction by BMP-4 in ventral mesoderm, Over-expression of GATA-2 in ventral mesoderm leads to increased globin production and forced expression of GATA-2 in primitive ectoderm adjacent to ventral mesoderm also stimulates globin expression. Our results suggest that BMP-4 and GATA-2 can function in two adjacent germ layers, mesoderm and ectoderm, to participate in blood cell formation during embryogenesis. (C) 1996 by The American Society of Hematology.

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  • Involvement of Ras/Raf/AP-1 in BMP-4 signaling during Xenopus embryonic development Reviewed

    RH Xu, ZG Dong, M Maeno, J Kim, A Suzuki, N Ueno, D Sredni, NH Colburn, HF Kung

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   93 ( 2 )   834 - 838   1996.1

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    Previously, we elucidated the role of bone morphogenetic protein 4 (BMP-4) in the dorsal-ventral patterning of the Xenopus embryo by using a dominant negative mutant of the BMP-4 receptor (DN-BR). The present paper describes the involvement of Pas, Raf, and activator protein 1 (AP-1) in BMP-4 signaling during Xenopus embryonic development, The AP-1 activity was determined by injecting an AP-1-dependent luciferase reporter gene into two-cell-stage Xenopus embryos and measuring the luciferase activity at various developmental stages. We found that injection of BMP-4 mRNA increased AP-1 activity, whereas injection of DN-BR mRNA inhibited AP-1 activity, Similar inhibitory effects were seen with injection of mRNAs encoding dominant negative mutants of c-Ha-Ras, c-Raf, or c-Jun, These results suggest that the endogenous AP-1 activity is regulated by BMP-4/Ras/Raf/Jun signals, We next investigated the effects of Ras/Raf/AP-1 signals on the biological functions of BMP-4. DN-BR-induced dorsalization of the embryo, revealed by the formation of a secondary body axis or dorsalization of the ventral mesoderm explant analyzed by histological and molecular criteria, was significantly reversed by coinjection of [Val(12)]Ha-Ras, c-Raf, or c-Jun mRNA, Furthermore, the BMP-4-stimulated erythroid differentiation in the ventral mesoderm was substantially inhibited by coinjection with the dominant negative c-Ha-Ras, c-Raf, or c-Jun mutant. Our results suggest the involvement of Ras/Raf/AP-1 in the BMP 4 signaling pathway.

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  • EXPRESSION OF AN AMPHIBIAN HOMOLOG OF THE EPH FAMILY OF RECEPTOR TYROSINE KINASES IS DEVELOPMENTALLY-REGULATED Reviewed

    TL JONES, KARAVANOVA, I, M MAENO, RC ONG, HF KUNG, IO DAAR

    ONCOGENE   10 ( 6 )   1111 - 1117   1995.3

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    In order to study the function of tyrosine kinase receptors during Xenopus development, we have isolated Xek (Xenopus Elk-like kinase), a tyrosine kinase receptor, which shows significant homology to rat Elk and chicken cek5, members of the Eph family. Xek exists as a maternally expressed mRNA which decreases in expression at the mid blastula transition and reappears at late neurulation in Xenopus, Xek mRNA is expressed at higher levels in the anterior and dorsal regions of embryonic stages 16, 24 and 37. In adult Xenopus tissues, Xek appears to be ubiquitously expressed with higher expression observed in brain and ovary, In situ hybridization analysis demonstrates localized mRNA expression in the brain, brachial arches, trigeminal facial ganglion, and the retina of the swimming tadpole stage of development. The similarities in sequence and expression pattern suggest that Xek is an amphibian member of the Eph family and may play a role in the development or function of the central nervous system.

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  • EXPRESSION OF THE HUMAN INTERLEUKIN-6 RECEPTOR ALPHA-CHAIN IN XENOPUS-LAEVIS OOCYTES Reviewed

    M EGAWA, M MAENO, HF KUNG, M SCHWABE

    CYTOKINE   7 ( 1 )   83 - 88   1995.1

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    We investigated the biochemical properties of the 80 kDa binding subunit (gp80) of the human interleukin 6 receptor (IL-6R) in the genetic environment of the amphibian Xenopus laevis. In vitro transcribed mRNA encoding full length human gp80 was microinjected into Xenopus laevis stage VI oocytes. Protein expression was monitored by iodinated IL-6 and human gp80-specific monoclonal antibodies (mAb) PM1 and MT18. Maximal IL-6 binding activity was observed between 36-42 h after injection. Scatchard analysis indicated that gp80-injected oocytes expressed two independent classes of IL-g binding sites of high- (K-d1 = 9 x 10(-11) M, 20 x 10(6) sites/cell) and low-affinity (K-d2 = 2 X 10(-9) M, 70.3 x 10(6) sites/cell). PM1 but not MT18 completely inhibited IL-6 binding to injected eggs. Our data suggest that the human IL-6R alpha-subunit gp80 is sufficient to confer high- and low-affinity IL-6 binding to Xenopus laevis oocytes.

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  • A TRUNCATED BONE MORPHOGENETIC PROTEIN-4 RECEPTOR ALTERS THE FATE OF VENTRAL MESODERM TO DORSAL MESODERM - ROLES OF ANIMAL POLE TISSUE IN THE DEVELOPMENT OF VENTRAL MESODERM Reviewed

    M MAENO, RC ONG, A SUZUKI, N UENO, HF KUNG

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   91 ( 22 )   10260 - 10264   1994.10

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    The biological effects of endogenous bone morphogenetic protein 4 (BMP-4), a member of the transforming growth factor beta family, on embryonic development of Xenopus laevis were investigated by using a functionally defective mutant of the BMP-4 receptor (Delta mTFR11), which blocks the BMP signaling pathway. Injection of Delta mTFR11 RNA into either the animal pale area or ventral marginal cells at the two-cell stage induced a dorsal phenotype in the explant of ventral mesoderm with animal pole tissue from stage 10+ embryo, even though the normal fate of this explant is a ''mesenchymal ball'' containing blood cells. These explants with the dorsal phenotype contained muscle, neural tissue, eye capsule, and cement gland. Northern blot analysis showed an increase of cardiac alpha-actin mRNA and a decrease of T alpha-globin mRNA expression, providing further evidence of a conversion from ventral to dorsal phenotype. Although injection of Delta mTFR11 RNA did not induce mesoderm in an animal cap culture, the same tissue injected with Delta mTFR11 RNA can alter the differentiation fate of uninjected ventral mesodermal explant from ventral to dorsal type, suggesting specific interaction of animal pole tissue and prospective ventral mesoderm in vivo.

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  • REGULATION OF PRIMARY ERYTHROPOIESIS IN THE VENTRAL MESODERM OF XENOPUS-GASTRULA EMBRYO - EVIDENCE FOR THE EXPRESSION OF A STIMULATORY FACTOR(S) IN ANIMAL POLE TISSUE Reviewed

    M MAENO, RC ONG, Y XUE, S NISHIMATSU, N UENO, HF KUNG

    DEVELOPMENTAL BIOLOGY   161 ( 2 )   522 - 529   1994.2

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    DOI: 10.1006/dbio.1994.1050

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  • CLONING AND EXPRESSION OF CDNA-ENCODING XENOPUS-LAEVIS BONE MORPHOGENETIC PROTEIN-1 DURING EARLY EMBRYONIC-DEVELOPMENT Reviewed

    M MAENO, Y XUE, TI WOOD, RC ONG, HF KUNG

    GENE   134 ( 2 )   257 - 261   1993.12

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    The Xenopus laevis DNA fragment encoding a protein homologous with human bone morphogenetic protein-1 (BMP-1) was amplified by polymerase chain reaction (PCR) from cDNA derived from stage 26 (st.26) embryonic RNA. Subsequently this fragment was used as a probe to isolate cDNA clones by screening of a X. laevis st.24 embryonic cDNA library. Two partial clones (22 and 63) were obtained and the missing 5'-end of the clone 22 was extended by the anchored PCR technique. The nucleotide sequence of the resulting clone (22AN) contained an open reading frame coding for a protein with 707 deduced amino acids. Three sizes of mRNA (2.9, 5.2 and 6.6 kb) were detected in blastula (st.9) and early gastrula (st.10) embryos, and in hatched tadpole (st.40), but little or no expression was observed in morula (st.7) and late gastrula (st.12) embryos, suggesting a physiological role(s) of X. laevis BMP-1 in normal embryonic development.

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  • MURINE STEM-CELL FACTOR STIMULATES ERYTHROPOIETIC DIFFERENTIATION OF VENTRAL MESODERM IN XENOPUS GASTRULA EMBRYO Reviewed

    RC ONG, M MAENO, HF KUNG

    EXPERIMENTAL CELL RESEARCH   205 ( 2 )   326 - 330   1993.4

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    DOI: 10.1006/excr.1993.1093

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  • POSITIVE AND NEGATIVE REGULATION OF THE DIFFERENTIATION OF VENTRAL MESODERM FOR ERYTHROCYTES IN XENOPUS-LAEVIS Reviewed

    M MAENO, RC ONG, HF KUNG

    DEVELOPMENT GROWTH & DIFFERENTIATION   34 ( 5 )   567 - 577   1992.10

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  • ANALYSIS OF ALLOTOLERANCE IN THYMECTOMIZED XENOPUS RESTORED WITH SEMIALLOGENEIC THYMUS GRAFTS Reviewed

    M MAENO, T NAKAMURA, S TOCHINAI, C KATAGIRI

    TRANSPLANTATION   44 ( 2 )   308 - 314   1987.8

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  • TOLERANCE INDUCED BY GRAFTING SEMI-ALLOGENEIC ADULT SKIN TO LARVAL XENOPUS-LAEVIS - POSSIBLE INVOLVEMENT OF SPECIFIC SUPPRESSOR-CELL ACTIVITY Reviewed

    T NAKAMURA, M MAENO, S TOCHINAI, C KATAGIRI

    DIFFERENTIATION   35 ( 2 )   108 - 114   1987

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  • DIFFERENTIAL COMMITMENT OF HEMATOPOIETIC STEM-CELLS LOCALIZED IN DISTINCT COMPARTMENTS OF EARLY XENOPUS EMBRYOS Reviewed

    C KATAGIRI, M MAENO, S TOCHINAI

    CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY   20   315 - 323   1986

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  • DIFFERENTIAL PARTICIPATION OF VENTRAL AND DORSOLATERAL MESODERMS IN THE HEMATOPOIESIS OF XENOPUS, AS REVEALED IN DIPLOID TRIPLOID OR INTERSPECIFIC CHIMERAS Reviewed

    M MAENO, S TOCHINAI, C KATAGIRI

    DEVELOPMENTAL BIOLOGY   110 ( 2 )   503 - 508   1985

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    DOI: 10.1016/0012-1606(85)90108-3

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  • THE LOCALIZATION OF PRECURSOR CELLS FOR LARVAL AND ADULT HEMATOPOIETIC-CELLS OF XENOPUS-LAEVIS IN 2 REGIONS OF EMBRYOS Reviewed

    M MAENO, A TODATE, C KATAGIRI

    DEVELOPMENT GROWTH & DIFFERENTIATION   27 ( 2 )   137 - 148   1985

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  • ELICITATION OF WEAK IMMUNE-RESPONSE IN LARVAL AND ADULT XENOPUS-LAEVIS BY ALLOGRAFTED PITUITARY Reviewed

    M MAENO, C KATAGIRI

    TRANSPLANTATION   38 ( 3 )   251 - 255   1984

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Books

  • Analyses of Immune Responses to Ontogeny-Specific Antigens using an Inbred Strain of Xenopus laevis (J Strain).

    Developmental Hematopoiesis: Methods in Molecular Medicine, The Humana Press Inc.  2004 

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  • 中胚葉系組織の分化機構-筋肉・血球の分化を誘導する分子相互作用-

    両生類の発生生物学(北海道大学出版会)  1998 

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MISC

  • Physiological importance of Xenopus Neptune in development of neural and neural crest cells

    Takayuki Kurauchi, Ai Araki, Yumi Izutsu, Mitsugu Maeno

    ZOOLOGICAL SCIENCE   22 ( 12 )   1464 - 1464   2005.12

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  • Characterization of embryonic non-lymphoid leukocytes in Xenopus laevis

    Sumihisa Tashiro, Yumi Izutsu, Mitsugu Maeno

    ZOOLOGICAL SCIENCE   21 ( 12 )   1301 - 1301   2004.12

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  • Physiological function of AP-2rep in early Xenopus embryo

    Yasutaka Ujiie, Masanori Gotoh, Yumi Izutsu, Mitsugu Maeno

    ZOOLOGICAL SCIENCE   21 ( 12 )   1298 - 1298   2004.12

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  • Isolation of adult immune cells rejected larval tail skin grafts from inbred strain of Xeaopus

    Ichiro Okano, Koki Fujiwara, Mitsugu Maeno, Yumi Izutsu

    ZOOLOGICAL SCIENCE   21 ( 12 )   1340 - 1340   2004.12

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  • DOWNREGULATION OF THE ANTIGEN GENE BY THYROID HORMONE DURING METAMORPHOSIS OF XENOPUS(Developmental Biology,Abstracts of papers presented at the 74^<th> Annual Meeting of the Zoological Society of Japan) :

    Fujii Hiroshi, Maeno Mitsugu, Izutsu Yumi

    Zoological science   20 ( 12 )   1560 - 1560   2003

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    Other Link: http://id.nii.ac.jp/1141/00037956/

  • THE REGULATORY MECHANISMS OF ENDOTHELIAL CELL DIFFERENTIATION IN XENOPUS EMBRYO(Developmental Biology)(Proceedings of the Seventieth Annual Meeting of the Zoological Society of Japan) :

    Saito Y., Kawakami M., Takeda M., Maeno M.

    Zoological science   16   81 - 81   1999

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    Other Link: http://id.nii.ac.jp/1141/00034582/

  • 両生類胚における造血発生

    細胞工学(透潤社)   17   1716 - 1721   1998

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  • 両生類胚における赤血球分化のプログラム「発生・神経研究の最前線96-'97」

    実験医学(羊土社)増刊号   14 ( 8 )   82 - 86   1996

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  • MECHANISM OF ALLOTOLERANCE IN XENOPUS .1. CLONAL ABORTION IN EARLY THYMECTOMIZED FROGS RECONSTITUTED BY TRANSPLANTATION OF IRRADIATED SEMIALLOGENEIC THYMUS

    M MAENO, T NAKAMURA, S TOCHINAI, C KATAGIRI

    ZOOLOGICAL SCIENCE   2 ( 6 )   902 - 902   1985

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  • MECHANISM OF ALLOTOLERANCE IN XENOPUS .2. ACTIVE SUPPRESSION OF RESPONSE AGAINST SKINS GRAFTED IN LARVAL STAGES

    T NAKAMURA, M MAENO, S TOCHINAI, C KATAGIRI

    ZOOLOGICAL SCIENCE   2 ( 6 )   902 - 902   1985

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  • DIFFERENTIATION POTENCY OF EMBRYONIC XENOPUS CELLS AS REVEALED BY INJECTION INTO BLASTOCOEL OF EARLY GASTRULAE

    M MAENO, C KATAGIRI

    DEVELOPMENT GROWTH & DIFFERENTIATION   27 ( 4 )   517 - 517   1985

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  • ANALYSES OF TOLERANT STATE INDUCED BY INJECTION OF BLASTOMERES INTO GASTRULAE OF XENOPUS-LAEVIS

    M MAENO, C KATAGIRI

    ZOOLOGICAL SCIENCE   1 ( 6 )   900 - 900   1984

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  • EMBRYONIC LOCALIZATION OF LYMPHOID AND ERYTHROID PRECURSOR CELLS IN XENOPUS-LAEVIS

    M MAENO, A TODATE, C KATAGIRI

    DEVELOPMENT GROWTH & DIFFERENTIATION   26 ( 4 )   394 - 394   1984

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Research Projects

  • Regulation of amphibian hematopoiesis: the distribution of hematopoietic stem cells in the liver, spleen, and bone marrow.

    Grant number:20K06729

    2020.4 - 2023.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

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  • 両生類で発見された新たな胚体起源に由来する骨髄球の性状と発生意義

    2016 - 2018

    System name:基盤研究(C)

    前野 貢

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  • Effects of neonicotinoid insecticides on paddy organisms, covering from individuals to biocommunity level

    Grant number:26281050

    2014.4 - 2017.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Sekijima Tsuneo

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    Grant amount:\16640000 ( Direct Cost: \12800000 、 Indirect Cost:\3840000 )

    The effects of insecticides for paddy rice on paddy organisms were evaluated from individuals to biocommunity level. Neonicotinoid insecticide, Clothanidin, gave several negative effects to paddy biocommunity, and particularly caused a decrease of the amount of midges, dragonflies, and water fleas. Also, Nereistoxin insecticide, Cartap, indused several severe abnormalities on earlier development of frog embryo including Xenopus. The DNA microarray analysis suggested that disturbance of the genes expression related to morphogenesis and immune system was involved in teratogenic process of frogs.

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  • 両生類胚における血島の分化制御に関する総合的研究

    2012 - 2014

    System name:基盤研究(C)

    前野 貢

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  • An acquired immune system involved in the tissue remodeling through self antigens

    Grant number:23370059

    2011.4 - 2015.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    IZUTSU YUMI, IWABUCHI Kazuya, ITO Michihiko, OKA Atsuko, MAENO Mitsugu

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    Grant amount:\19890000 ( Direct Cost: \15300000 、 Indirect Cost:\4590000 )

    Vertebrate ontogenesis, including Xenopus frogs, shows morphological changes from embryonic- (larval-) organs into the adult counterparts. This process is called tissue remodeling. The most drastic remodeling is seen in the tadpole tail regression during amphibian metamorphosis. We have previously proposed a new model that the adult-type immune cells, which are newly differentiated during metamorphosis, recognize and remove own tail tissues as non-self. We have isolated two genes encoding the antigen proteins, Ouro1 and Ouro2, as targets for adult immune T cells. In this study, to clarify function of T cells vs these Ouro1 and Ouro2 antigens, we analyzed gain- and loss-of function of T cells. Results suggest that T cells are nessesorry and sufficient for the regression of tadpole tails expressing both Ouro1 and Ouro2 antigen proteins.

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  • 両生類胚の腹部血島の分化にかかわる新たな因子の同定と解析

    2009 - 2011

    System name:基盤研究(C)

    前野 貢

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    Authorship:Principal investigator  Grant type:Competitive

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  • 組織特異的発現を示すKruppel型転写因子の胚発生における役割

    2004 - 2005

    System name:基盤研究(C)

    前野 貢

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  • Regulation of blood and vascular cell differentiation in embryos

    Grant number:13680802

    2001 - 2002

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    MAENO Mitsugu

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    Grant amount:\2500000 ( Direct Cost: \2500000 )

    In order to determine the tissue interactions that propagate blood formation in amphibian embryogenesis, we used embryos that had the vegetal cytoplasm removed. These embryos displayed a marked enhancement of globin expression. Several lines of experimental evidence demonstrate the critical role of animal pole-derived ectoderm in blood cell formation: 1) Mesoderm derived from dorsal blastomeres injected with galactosidase mRNA (as a lineage tracer) expressed globin when interfaced with an animal pole-derived ectodermal layer: 2) Embryos in which the animal pole tissue had been removed by dissection at the blastula stage failed to express globin: 3) Exogastrulated embryos that lacked an interaction between the mesodermal and ectodermal layers failed to form blood cells, while, muscle cells were observed in these embryos. These observations suggest that default mesodermal cells need an additional BMP-4-dependent factor from the overlying ectoderm for further differentiation into a blood cell lineage.
    Further experiments were done to elucidate the relationship between blood and vascular cell differentiation in the ventral blood island mesoderm. Using Xtie-2, as a vascular cell maker, it was shown that BMP (bone morphogenetic protein) signal is essential for both blood and vascular cell differentiation. On the other hand, FGF (fibroblast growth factor) signal was shown to control the distinct localization of vascular and blood cells. Therefore this study suggests that the early steps of blood and vascular cell differentiation are regulated by a common BMP-4-dependent signaling; however, distinct factor(s) such as FGF are involved in different distribution of these two cell lineages.

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  • REGULATORY MECHANISMS OF DORSO-VENTRAL AXIS FORMATION IN AMPHIBIAN EMBRYO.

    Grant number:09680721

    1997 - 1999

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    MAENO Mitsugu

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    Grant amount:\2700000 ( Direct Cost: \2700000 )

    I have investigated several cDNA clones, which encode for ventralizing agents. Among these factors, the roles of msx-1 and msx-2 in the dorsoventral axis formation have been extensively analyzed. These transcriptional repressor proteins were expressed in presumptive ectoderm and mesoderm ventrally, but not dorsally, at gastrula stage. Both msx-1 and msx-2 possessed a similar ventralizing activity, but that of msx-2 was higher than of msx-1, as revealed by the injection of RNA into dorsal blastomeres. The secondary axis induced by the injection of tBR was rescued by simultaneous injection of msx-1/msx-2. Furthermore, if VP-16/msx-1 fusion RNA, which was expected to function as a dominant negative msx-1, was injected into the ventral blastomeres, partial Secondary axis was formed. Therefore, msx-1 and msx-2 transduce a main tract of BMP-4 signaling. Msx factors also have a role in neural tissue induction in ectodermal cells. If msx-1 was coinjected with neural inducer genes such as noggin or cerberus, the expression of N-CAM was completely suppressed. As also shown in tBR (which directly induces neural tissue in animal cap), VP 16/msx-1 fusion RNA was able to induce neural tissue directly in animal cap cells. The results indicate that msx proteins play a central role in establishing dorso-ventral axis and in neural tissue formation in gastrulating embryo, by antagonizing the expression of organizer genes. The expression and function of GATA-1 (another transcriptional regulator) and BMP-1 (metalloprotease) in Xenopus embryo have been also investigated in this study.

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  • Molecular mechanism of hematopoietic and angiopoietic differentiation in embryo

    1992 - 2004

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    Grant type:Competitive

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  • Experimental Infection and Characterization of Epidemic Non-A, Non-B Hepatitis Virus.

    Grant number:63480146

    1988 - 1990

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for General Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    SHIKATA Toshio, MAENO Mitsugu, SUZUKI Koyu, ESUMI Mariko, UCHIDA Toshikazu

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    Grant amount:\7000000 ( Direct Cost: \7000000 )

    An attempt was made to establish the animal model of epidemic non-A, non-B hepatitis. Cynomolgus macaca was a good animal model, because if we inoculate enough amount virus intravenously, almost all monkeys developed acute hepatits. Serial transmission experiments were also done successfully. We have found large amount of virus excrete into bile from 10 days after inoculation until peak of transaminase. In early stage, virus scattered in the bile but next stage virus particles spontaneously aggregated probably due to secretory IgA. We already cloned viral RNA from lambda gt11 cDNA library using immunoscreening method. We also confirmed viremia in incubation stage by PCR method. Now we are preparing antibody assay kit using recombinant peptide. We are attempting to debelop recombinant vaccine too.

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  • Serological diagnosis of non-A, non-B hepatitis.

    Grant number:62870018

    1987 - 1989

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Developmental Scientific Research

    Awarding organization:Japan Society for the Promotion of Science

    SHIKATA Toshio, MAENO Mitsugu, SUZUKI Koyu, ESUMI Mariko, UCHIDA Toshikazu, SHIMIZU Yohko

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    Grant amount:\7600000 ( Direct Cost: \7600000 )

    An attempt was made to establish an antigen antibody assay system associated with non-A, non-B hepatitis. We have established monoclonal antibody from convalescent chimpanzee lymphocytes by EV virus transformation method. We found the corresponding antigen in the chimpanzee liver infected with non-A, non-B hepatitis virus and never found in the liver of the chimpanzees infected hepatitis A and B virus.
    However, cDNA coding this antigen hybridized with somatic genome, then this antigen was not coded by the viral genome.
    Then we cloned hepatitis C Genome from Japanese donor blood by immunoscreening and sequenced. Sequence of this Japanese clone of HCV is different from Chiron's clone. Hemology is only 74% in region NS5. We established EIA assay system of the antibody against HCV.
    And we also established cDNA assay system of HCV genom by PCR method.

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  • Development of a cytofluorometry system for tissue culture cells in vivo

    Grant number:62870017

    1987 - 1989

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Developmental Scientific Research

    Awarding organization:Japan Society for the Promotion of Science

    ASHIHARA Tsukasa, KONISHI Eiichi, HOSOKAWA Youhei

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    Grant amount:\3900000 ( Direct Cost: \3900000 )

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  • Electron microscopic investigation of ribonucleic acid in nuclear particulate aggregates of hepatitis NANB by means of nuclease-gold complexes.

    Grant number:62570315

    1987 - 1988

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for General Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    KOJIMA Takashi, SUGITANI Masahiko, SUZUKI Koyu, MAENO Mitsugu

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    Grant amount:\2100000 ( Direct Cost: \2100000 )

    The ultrastructural localization of hepatitis delta antioen (HDAg) and ribonucleic acid (RNA) was investigated by immunoperoxidase electron microscopy and by enzyme electron microscopy of RNase-gold complexes on liver biopsies from seven patients with hepatitis D. HDAh was mainly localized in the nucleus, and sometimes in the cytoplasm of hepatocytes. Ultrastructurally, intranuclear HDAg was found on nuclear particulate structures measuring 20-to 30-nm in diameter. Intranuclear RNA visualized with gold particles was found in high amounts in the nucleolus, to a small extent in the chromatin area and in addition also on nuclear particulate structures. These findings suggest that intranuclear aggregates of irregular granular particulate structures in hepatitis D are the internal component of HDV particles in blood.
    In order to clarify the hepatitis non-A, non-B virus (H-NANB-V), enzyme electron microscopy of RNase-gold complexes on liver biopsies from two chimpanzees experimentally infected hepatitis HANB. Nuclear particulate structures, curved membrane and double unit membrane were found in all two biopsy speciment. Although the nuclear particulate structures were closely associated with RNA as in hepatitis D, curved membrane and double unit membrane were not related with nucleic acids of RNA and deoxi-ribonucleic acid (DNA). To date, no particulate structures specifically associated with H-NANB-V were demonstrated by enzyme electron microscopy.

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Teaching Experience

  • 地域創生科学演習

    2022
    Institution name:新潟大学

  • 生物学実習I

    2022
    Institution name:新潟大学

  • 生物学実習II

    2022
    Institution name:新潟大学

  • 基礎生物科学実習II

    2022
    Institution name:新潟大学

  • 基礎生物科学実習I

    2022
    Institution name:新潟大学

  • 理学スタディ・スキルズ

    2021
    Institution name:新潟大学

  • 生物学特論II

    2021
    Institution name:新潟大学

  • 先端科学技術総論

    2021
    Institution name:新潟大学

  • 日本事情自然系A

    2021
    Institution name:新潟大学

  • 胚発生学特論

    2021
    Institution name:新潟大学

  • 課題研究II(生物学)

    2018
    Institution name:新潟大学

  • 生物学総合演習

    2017
    Institution name:新潟大学

  • 自然科学基礎実験

    2017
    Institution name:新潟大学

  • 課題研究I(生物学)

    2017
    Institution name:新潟大学

  • 生物学基礎実習a

    2017
    Institution name:新潟大学

  • 生物学基礎演習

    2017
    Institution name:新潟大学

  • 生物学特論Ⅲ

    2015
    Institution name:新潟大学

  • 科学・技術と社会

    2013
    -
    2015
    Institution name:新潟大学

  • Biology Today

    2013
    Institution name:新潟大学

  • 生命科学への招待(生物学学習法)

    2013
    Institution name:新潟大学

  • 発生生物学II

    2012
    Institution name:新潟大学

  • 課題研究I(生物学科)

    2012
    -
    2016
    Institution name:新潟大学

  • 生命・食料科学特定研究BⅡ

    2012
    -
    2014
    Institution name:新潟大学

  • 研究発表演習(中間発表)

    2012
    -
    2014
    Institution name:新潟大学

  • 生命・食料科学セミナーBⅡ

    2012
    -
    2014
    Institution name:新潟大学

  • 文献詳読Ⅱ

    2012
    -
    2014
    Institution name:新潟大学

  • 研究発表(博士)演習(学会発表含む)

    2012
    -
    2013
    Institution name:新潟大学

  • 生命・食料科学特定研究BⅠ

    2012
    -
    2013
    Institution name:新潟大学

  • 文献詳読Ⅰ

    2012
    -
    2013
    Institution name:新潟大学

  • 基礎生命科学(博士)演習(中間発表)

    2012
    -
    2013
    Institution name:新潟大学

  • 生命・食料科学セミナーBⅠ

    2012
    -
    2013
    Institution name:新潟大学

  • 外国語論文解説・討論Ⅰ

    2012
    Institution name:新潟大学

  • リサーチキャンプ

    2012
    Institution name:新潟大学

  • 生命・食料科学博士特定研究Ⅰ

    2012
    Institution name:新潟大学

  • 生命・食料科学博士セミナーⅠ

    2012
    Institution name:新潟大学

  • 自然科学総論Ⅳ

    2012
    Institution name:新潟大学

  • 生物学特論IV B

    2011
    Institution name:新潟大学

  • 基礎生物科学実習II

    2009
    -
    2022
    Institution name:新潟大学

  • 日本事情自然系A

    2009
    -
    2021
    Institution name:新潟大学

  • 生物学実験 I

    2008
    -
    2018
    Institution name:新潟大学

  • 発生生物学

    2008
    -
    2009
    Institution name:新潟大学

  • 生物学特論V A

    2008
    Institution name:新潟大学

  • 動物形態発生学実習

    2007
    Institution name:新潟大学

  • 発生生物学演習

    2007
    Institution name:新潟大学

  • 基礎細胞遺伝学

    2007
    Institution name:新潟大学

  • 生物学基礎B

    2007
    -
    2022
    Institution name:新潟大学

  • 基礎生物科学実習I

    2007
    -
    2022
    Institution name:新潟大学

  • 胚発生学

    2007
    -
    2021
    Institution name:新潟大学

  • 胚発生学特論

    2007
    -
    2021
    Institution name:新潟大学

  • 課題研究II

    2007
    -
    2014
    Institution name:新潟大学

  • 発生のプログラム

    2007
    -
    2011
    Institution name:新潟大学

  • 課題研究I

    2007
    -
    2011
    Institution name:新潟大学

  • 分子生物学実習

    2007
    Institution name:新潟大学

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