Updated on 2024/04/16

写真a

 
IZUTSU-SHISHIDO Yumi
 
Organization
Academic Assembly Institute of Science and Technology CHIKYU SEIBUTSU KAGAKU KEIRETU Professor
Faculty of Science Professor
Graduate School of Science and Technology Life and Food Sciences Professor
Title
Professor
Other name(s)
SHISHIDO Yumi
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Degree

  • Ph.D. (Biology) ( 1993.3   Hiroshima University )

Research Interests

  • 機能生物化学

  • 免疫学

  • 発生生物学

Research Areas

  • Life Science / Immunology

  • Life Science / Developmental biology

  • Life Science / Structural biochemistry

Research History (researchmap)

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

    2018.5

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  • Niigata University   Faculty of Science   Professor

    2018.5

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  • Niigata University   Faculty of Science   Associate Professor

    2012.4 - 2018.4

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

    2012.4 - 2018.4

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  • Niigata University   Faculty of Science Department of Biology   Assistant Professor

    2007.4 - 2012.3

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  • Niigata University   Faculty of Science   Assistant

    2004.4 - 2007.3

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  • Niigata University   Graduate School of Science and Technology   Assistant

    1999.10 - 2004.3

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  • 北海道大学免疫科学研究所   助手

    1998.4 - 1999.10

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  • 北海道大学免疫科学研究所   研究員

    1996.9 - 1998.3

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  • Hokkaido University   Special researcher of the Japan Society for the Promotion of Science

    1994.4 - 1996.8

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Research History

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

    2018.5

  • Niigata University   Faculty of Science   Professor

    2018.5

  • Niigata University   Faculty of Science   Associate Professor

    2012.4 - 2018.4

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

    2012.4 - 2018.4

  • Niigata University   Faculty of Science Department of Biology   Assistant Professor

    2007.4 - 2012.3

  • Niigata University   Faculty of Science   Research Assistant

    2004.4 - 2007.3

  • Niigata University   Graduate School of Science and Technology   Research Assistant

    1999.10 - 2004.3

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Education

  • Hiroshima University   Graduate School, Division of Natural Science   Zoological Department

    - 1993.3

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    Country: Japan

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  • Tokyo Metropolitan University   理学部生物学科

    - 1990.3

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    Country: Japan

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Professional Memberships

Qualification acquired

  • First Kind of High School Teacher License

  • First Kind of Junior High School Teacher License

 

Papers

  • Cells from subcutaneous tissues contribute to scarless skin regeneration in Xenopus laevis froglets Reviewed

    Otsuka-Yamaguchi R, Kawasumi-Kita A, Kudo N, Izutsu Y, Tamura K, Yokoyama H

    Dev. Dyn.   248   586 - 597   2017

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

    DOI: 10.1002/dvdy.24520.

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  • Genome evolution in the allotetraploid frog Xenopus laevis Reviewed

    Adam M. Session, Yoshinobu Uno, Taejoon Kwon, Jarrod A. C. Hapman, Atsushi Toyoda, Shuji Takahashi, Akimasa Fukui, Akira Hikosaka, Atsushi Suzuki, Mariko Kondo, Simon J. van Heeringen, Ian Quigley, Sven Heinz, Hajime Ogino, Haruki Ochi, Uffe Hellsten, Jessica B. . Lyons, Oleg Simakov, Nicholas Putnam, Jonathan Stites, Yoko Kuroki, Toshiaki Tanaka, Tatsuo Michiue, Minoru Watanabe, Ozren B. Ogdanovic, Ryan Lister, Georgios Georgiou, Sarita S. Paranjpe, Ila Van Kruijsbergen, Shengquiang Shu, Joseph Carlson, Tsutomu Kinoshita, Yuko Ohta, Shuuji Mawaribuchi, Jerry Jenkins, Jane Grimwood, Jeremy Schmutz, Therese Mitros, Sahar V. Mozaffari, Yutaka Suzuki, Yoshikazu Haramoto, Takamasa S. Yamamoto, Chiyo Takagi, Rebecca Heald, Kelly Miller, Christian Haudenschild, Jacob Kitzman, Takuya Nakayama, Yumi I. Zutsu, Jacques Robert, Joshua Fortriede, Kevin Burns, Vaneet Lotay, Kamran Karimi, Yuuri Yasuoka, Darwin S. Dichmann, Martin F. Flajnik, Douglas W. Houston, Jay Shendure, Louis DuPasquier, Peter D. Vize, Aaron M. Zorn, Michihiko Ito, Edward M. Marcotte, John B. . Wallingford, Yuzuru Ito, Makoto Asashima, Naoto Ueno, Yoichi Matsuda, Gert Jan C. . Veenstra, Asao Fujiyama, Richard M. Harland, Masanori Taira, Daniel S. Rokhsar

    NATURE   538 ( 7625 )   336 - +   2016.10

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    To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.

    DOI: 10.1038/nature19840

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  • Molecular evolution of two distinct dmrt1 promoters for germ and somatic cells in vertebrate gonads. Reviewed

    Mawaribuchi S, Musashijima M, Wada M, Izutsu Y, Kurakata E, Park M. K, Takamatsu N, Ito M

    Mol. Biol. Evol.   34   724 - 733   2016

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    DOI: 10.1093/molbev/msw273.

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

    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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  • Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis Reviewed

    C. Tomiyama, H. Watanabe, Y. Izutsu, M. Watanabe, T. Abo

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY   166 ( 2 )   258 - 268   2011.11

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

    Concanavalin A (Con A)-induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c(+) I-Alow B220(+)); however, conventional DC were CD11c(+) I-Ahigh B220(-). At an early stage (3-6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12-24 h) in parallel with hepatic failure. The hepatic CD11c(+) DC population contained many CD11b-cells, while the majority of splenic CD11c(+) DC were CD11b(+). After Con A administration, the proportion of I-A(+) and CD11b(+) cells within the CD11c(+) DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c(+) DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)-12 and IL-2, rather than modulating effector cell function.

    DOI: 10.1111/j.1365-2249.2011.04458.x

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  • Opposite roles of DMRT1 and its W-linked paralogue, DM-W, in sexual dimorphism of Xenopus laevis: implications of a ZZ/ZW-type sex-determining system Reviewed

    Shin Yoshimoto, Nozomi Ikeda, Yumi Izutsu, Tadayoshi Shiba, Nobuhiko Takamatsu, Michihiko Ito

    DEVELOPMENT   137 ( 15 )   2519 - 2526   2010.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:COMPANY OF BIOLOGISTS LTD  

    A Y-linked gene, DMY/dmrt1bY, in teleost fish medka and a Z-linked gene, DMRT1, in chicken are both required for male sex determination. We recently isolated a W-linked gene, DM-W, as a paralogue of DMRT1 in Xenopus laevis, which has a ZZ/ZW-type sex-determining system. The DNA-binding domain of DM-W shows high sequence identity with that of DMRT1, but DM-W has no significant sequence similarity with the transactivation domain of DMRT1. Here, we first show colocalization of DM-W and DMRT1 in the somatic cells surrounding primordial germ cells in ZW gonad during sex determination. We next examined characteristics of DM-W and DMRT1 as a transcription factor in vitro. DM-W and DMRT1 shared a DNA-binding sequence. Importantly, DM-W dose-dependently antagonized the transcriptional activity of DMRT1 on a DMRT1-driven luciferase reporter system in 293 cells. We also examined roles of DM-W or DMRT1 in gonadal formation. Some transgenic ZW tadpoles bearing a DM-W knockdown vector had gonads with a testicular structure, and two developed into frogs with testicular gonads. Ectopic DMRT1 induced primary testicular development in some ZW individuals. These observations indicated that DM-W and DMRT1 could have opposite functions in the sex determination. Our findings support a novel model for a ZZ/ZW-type system in which DM-W directs female sex as a sex-determining gene, by antagonizing DMRT1. Additionally, they suggest that DM-W diverged from DMRT1 as a dominant-negative type gene, i.e. as a 'neofunctionalization' gene for the ZZ/ZW-type system. Finally, we discuss a conserved role of DMRT1 in testis formation during vertebrate evolution.

    DOI: 10.1242/dev.048751

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  • 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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    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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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATL ACAD SCIENCES  

    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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  • おたまじゃくしの尾はなぜ消えるのですか?

    井筒 ゆみ

    STAFF News letter   20 ( 12 )   6 - 6   2009.10

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  • 免疫学的な観点から見るツメガエルの発生

    井筒 ゆみ

    ISI News letter   17 ( 2 )   18 - 19   2009.10

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

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

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

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

    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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  • The immune system is involved in Xenopus metamorphosis Reviewed

    Yumi Izutsu

    FRONTIERS IN BIOSCIENCE   14   141 - 149   2009.1

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    Amphibian metamorphosis provides a model to elucidate the mechanisms underlying how vertebrates reconstitute a body plan and how the immune system develops during ontogeny. In Xenopus, T cells are expanded from the early developmental stages just after hatching. These T cells switch from larval-type in an easily tolerizable state into an adult-type having a potent immune responsiveness comparable to that of mammals. During metamorphosis, tadpoles exhibit morphological changes in skin that completely transforms from larval-type to adult-type. Only tail tissue behaves differently; it remains a larval-type tissue until it disappears at the end of metamorphosis. Thus, at metamorphic climax, four different types of cells co-exist in a tadpole body: larval tissue cells; adult tissue cells; larval immune cells; and adult immune cells. Based on the results showing that tadpole tail skin is rejected by syngeneic adult, it is proposed that the elimination of the larval tissue cells by the adult T cells that occurs during metamorphosis is immunologically mediated. Recent results indicate that the antigenic proteins expressed in the metamorphosing skin cells participate in the process of tail regression. This chapter describes how animals adjust and survive through such crises associated with large scale replacement of entire body cells.

    DOI: 10.2741/3235

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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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  • おたまじゃくしの尾はなぜ消える?/免疫学の視点から

    井筒 ゆみ

    ミクロスコピア   23   15 - 21   2006.12

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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 Maéno

    Development Growth and Differentiation   48 ( 8 )   499 - 512   2006.10

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    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. © 2006 The Authors.

    DOI: 10.1111/j.1440-169X.2006.00885.x

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

    Izutsu Y, Maeno M

    Methods. Mol. Med.   105   149 - 158   2005.12

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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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  • 近交系アフリカツメガエルを用いた発生段階特異的な抗原の検出法と組織リモデリングへのアプローチ

    井筒 ゆみ

    遺伝子医学別冊   44 - 49   2003.12

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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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  • 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

    Mikihito Watanabe, Madoka Ohshima, Miyuki Morohashi, Mitsugu Maéno, Yumi Izutsu

    Development Growth and Differentiation   45 ( 1 )   77 - 84   2003.2

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

    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.

    DOI: 10.1046/j.1440-169X.2003.00676.x

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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.

    DOI: 10.1046/j.1440-169X.2002.00660.x

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

    Fumie Iraha, Yoshinari Saito, Keiko Yoshida, Masatoki Kawakami, Yumi Izutsu, Ira Owen Daar, Mitsugu Maéno

    Development Growth and Differentiation   44 ( 5 )   395 - 407   2002

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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 α-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 α-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 α-globin were markedly induced in ectodermal explants (animal caps) from embryos co-injected with activin andbone morphogenetic protein (BMP)-4 RNA. Furthermore, both Xtie-2 and α-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.

    DOI: 10.1046/j.1440-169X.2002.00653.x

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

    Kikkawa M, Yamazaki M, Izutsu Y, Maéno M

    Int. J. Dev. Biol.   45   387 - 396   2001.12

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  • Larval antigen molecules recognized by adult immune cells of inbred Xenopus laevis: Two pathways for recognition by adult splenic T cells Reviewed

    Yumi Izutsu, Shin Tochinai, Kazuya Iwabuchi, Kazunori Onoè

    Developmental Biology   221 ( 2 )   365 - 374   2000.5

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    During anuran metamorphosis, larval cells of the tadpole are completely eliminated and replaced by adult cells in the corresponding tissues of the frog for the adaptation to terrestrial life from an aquatic life. Before the metamorphic climax, most of the cells have already transformed from larval cells into adult-type cells, but the tail cells remain as larval cells even at the climax stages of metamorphosis. In our previous works, we demonstrated that larval skin grafts are rejected by an inbred strain of adult Xenopus and that the larval cells are recognized and made apoptotic by splenocytes obtained from adults and/or metamorphosing tadpoles in vitro (Y. Izutsu and K. Yoshizato, 1993, J. Exp. Zool. 266, 163-167
    Y. Izutsu et al., 1996, Differentiation 60, 277-286). In the present study, it was found that there were two types of larval epidermal cells, classified according to the presence of major histocompatibility complex (MHC)
    one is the apical cell expressing both MHC classes I and II, and the other is the skein cell, which expresses no MHC. By a Percoll gradient, we were able to separate these two types of cells and examined the proliferative response of adult T cells to each of them. It was revealed that the apical cells (MHC-positive) were recognized directly by adult splenic T cells, whereas the skein cells (MHC- negative) were recognized by the T cells via the antigen presentation by adult splenocytes. Both of these proliferative responses were restricted to MHC class II. This is the first report showing how the larval-specific antigens present in different forms in epidermal cells are recognized as immunological targets by syngeneic adult T lymphocytes. (C) 2000 Academic Press.

    DOI: 10.1006/dbio.2000.9681

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  • Loss of reactivity to pan-cadherin antibody in epidermal cells as a marker for metamorphic alteration of Xenopus skin Reviewed

    Yumi Izutsu, Shin Tochinai, Kazunori Onoé

    Development Growth and Differentiation   42 ( 4 )   377 - 383   2000

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    Pan-cadherin antibodies recognize the conserved C-terminal region of the family of cell-cell adhesion molecules, cadherins, and have a broad spectrum of reactivity to the molecules. In the present study, by immunohistochemistry using an anti-pan cadherin monoclonal antibody (mAb), expression dynamics of cadherins in epidermal tissues were analyzed during metamorphosis of Xenopus laevis. At early stages of development, the anti-pan cadherin mAb detected signals at cell-cell boundaries and in the cytoplasm of both trunk and tail epidermal cells. During metamorphosis, the immunoreactivity decreased in the trunk skin tissue but remained in the tail. At the climax stage, immunoreactivity was observed only in the regressing tail epidermis. The signals disappeared completely from the trunk epidermis, which had already transformed into adult-type tissue. This observation was confirmed by western blot analysis. A specific band was detected in the larval skin, but not in the adult lysate, at approximately 135kDa in molecular size, corresponding to the molecular mass of cadherins. This different immunoreactivity in larvae and adults was observed in the epidermis of the skin, but not in any other tissues examined, that is, brain, kidney and liver. The immunoreactivity seen in larval epidermal cells was drastically downregulated by thyroid hormone treatment in vitro. These changes of immunoreactivity were specific for the C-terminal region of cadherins, suggesting intracellular alteration of the molecules during metamorphosis, and the anti-pan cadherin mAb can be a marker for larval-type epidermal cells that is applicable to analysis of Xenopus metamorphosis.

    DOI: 10.1046/j.1440-169X.2000.00527.x

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  • Adult-type splenocytes of Xenopus induce apoptosis of histocompatible larval tail cells in vitro Reviewed

    Y Izutsu, K Yoshizato, S Tochinai

    DIFFERENTIATION   60 ( 5 )   277 - 286   1996.9

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    Larval cells of the anuran tadpole are replaced by adult cells in the corresponding tissues of the frog during metamorphosis: tissues of the tail, which have no counterpart in the adult, are completely eliminated during metamorphosis. We have previously demonstrated that young adults of the major histocompatibility complex (MHC) homozygous inbred J strain of Xenopus laevis reject skin grafts from larvae of the same strain, showing that there is histoincompatibility between larval and adult skin tissues [19]. Thus, we postulated that some immunological recognition might be involved in this specific elimination of the tail tissue and set out to test the idea. Using in vitro assays, we detected a significant increase in proliferation of splenocytes derived from adult and metamorphic climax animals co-cultured with larval tail tissue. This response was shown to be thymus-dependent. However, the degeneration of larval tissues was not observed in such co-cultures under our standard culture conditions. To detect the possible cytotoxicity of splenocytes, the culture conditions were modified by supplementing with 10% heat-inactivated adult Xenopus serum instead of 10% fetal calf serum (FCS). After this modification, the degeneration of larval tissues was observable macroscopically and microscopically with cocultured adult splenocytes, but not tadpole ones. The nuclear fragmentation of the epidermal cells was seen by light and electron microscopy. Apoptosis was evidenced by the demonstration of the ''ladder pattern'' upon electrophoresis of genomic DNA obtained from the degenerating larval tissues. Surprisingly, this response was thymus independent. Moreover, it was shown that this response was not observed when the larval tissues were cultured with adult thymocytes or adult epidermal cells. In vivo, migration of T cells into the epidermis of tail tissues at the late climax of metamorphosis was demonstrated immunohistochemically using a monoclonal antibody against Xenopus T cells, even in the early thymectomized tadpoles. Considering these results, we propose that populations of adult-type non-T leukocytes might participate in the specific detection and elimination of larval type cells during metamorphosis.

    DOI: 10.1046/j.1432-0436.1996.6050277.x

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  • METAMORPHOSIS-DEPENDENT RECOGNITION OF LARVAL SKIN AS NON-SELF BY INBRED ADULT FROGS (XENOPUS-LAEVIS) Reviewed

    Y IZUTSU, K YOSHIZATO

    JOURNAL OF EXPERIMENTAL ZOOLOGY   266 ( 2 )   163 - 167   1993.6

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    Larval cells in tissues of the anuran tadpole are replaced by adult cells in the corresponding tissue of the frog during metamorphosis. As an extreme example of such replacement, tissues of the tail, which have no counterpart in the adult, are completely eliminated during metamorphosis. We postulated that some immunological recognition mechanism might be involved in this specific elimination of the tail tissue. Our working hypothesis was tested by applying the skin transplantation technique to individuals of the inbred J strain of Xenopus laevis, which accept homografts. We demonstrated that young adults reject skin grafts from larvae. This rejection was immunological in nature because the secondary response of rejection was observed. There was a clear difference in graft rejection between grafts from the tail and those from the body. Grafts of tail skin were rejected irrespective of the metamorphic stages of donors. By contrast, grafts of body skin became acceptable as donors metamorphosed. The mean survival time of the larval skin was much longer than that of major histocompatibility complex (MHC)-disparate skin grafts reported by other investigators, suggesting that the rejection described in the present study is due to disparity in minor histocompatible (minor-H) antigens. We propose the involvement of the immunological recognition mechanism in the process of specific detection and elimination of larval cells in the tail.

    DOI: 10.1002/jez.1402660211

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  • EPIDERMAL-CELLS OF THE TAIL OF AN ANURAN LARVA ARE COMPETENT TO TRANSFORM INTO THE ADULT-TYPE CELLS Reviewed

    K YOSHIZATO, A NISHIKAWA, Y IZUTSU, M KAIHO

    ZOOLOGICAL SCIENCE   10 ( 1 )   183 - 187   1993.2

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    The epidermis of an anuran tadpole shows the region-specific metamorphic fate: the body epidermis transforms into the adult epidermis, while the tail epidermis commits apoptosis. The only explanation for this difference has been that the tail lacks basal cells which are competent to transform into germinative cells of the adult epidermis. Human blood group antigen A was found to be a specific molecular marker for adult-type epidermal cells. A sharp threshold was apparent at the body-tail junction in expression of the antigen. Utilizing this marker, we succeeded in demonstrating the presence of a specific population of epidermal cells in the tail which can differentiate into the adult-type germinative cells under the direct action of thyroid hormone. This was an unexpected result in that the tail makes provision for the adult life. We propose a hypothesis on the regulation of region-specific metamorphic changes of the anuran larval epidermis.

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  • Differential distribution of epidermal basal cells in the anuran larval skin correlates with the skin's region-specific fate at metamorphosis. Reviewed

    Izutsu Y, Kaiho K, Yoshizato K

    J. Exp. Zool.   267   605 - 615   1993

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MISC

Presentations

  • Immune antigen proteins Ouro1 and Ouro2 for tadpole tail degeneration in Xenopus metamorphosis International conference

    「Izutsu Y」「Kikuta T」「Kazama Y」「Maeno M」

    International Xenopus Conference  2012.9 

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    Venue:フランス  

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  • トランスジェニックXenopusラインの樹立への近道

    屋井潮美, 井筒ゆみ

    第5回XCIJ首都圏支部会研究集会  2011.12 

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  • ツメガエル尾部抗原タンパク質Ouroに対するT細胞の増殖反応

    風間勇太, 井筒ゆみ

    第5回XCIJ首都圏支部会研究集会  2011.12 

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  • Immune system involved in the cell death via Ouro antigen proteins during amphibian metamorphosis International conference

    2011.9 

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  • Immune system involved in the cell death during vertebrate organogenesis

    2011.8 

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  • Immune system involved in the cell death during Xenopus metamorphic tail regression International conference

    Yumi Izutsu

    7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology (ISAREN)  2011.7 

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    Venue:University of Michigan, Ann Arbor, USA  

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  • The role of the immune system in the tail tissue degeneration during amphibian metamorphosis

    井筒 ゆみ

    第33回日本分子生物学会  2010.12 

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    Venue:神戸ポートアイランド、神戸  

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  • Changes of intracellular localizations of the tail antigen protein Ouro in cultured XenopusA6 cells

    2010.9 

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  • A role of the immune system in the tadpole tail degeneration during Xenopus metamorphosis International conference

    Yumi Izutsu, Tomomi Oshima, Shin-ichiro Hayashida, Akira Hanasaki, Mitsugu Maéno

    13th International Xenopus Conference  2010.9 

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    Venue:Lake Louise, Alberta, Canada  

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  • Knockdown of ouro genes inhibit tadpole tail regression during Xenopus metamorphosis International conference

    Akira Hanasaki, Mitsugu Maéno, Yumi Izutsu

    13th International Xenopus Conference  2010.9 

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    Venue:Lake Louise, Alberta, Canada  

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  • A possible reason why both ouro1 and ouro2 genes are required for tail regression during Xenopus metamorphosis International conference

    Tomomi Oshima, Mitsugu Maéno, Yumi Izutsu

    13th International Xenopus Conference  2010.9 

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    Venue:Lake Louise, Alberta, Canada  

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Research Projects

  • 上皮組織リモデリングにおける自己抗原タンパク質を介したT細胞の分子認識機構

    2018.4 - 2021.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    井筒ゆみ

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  • 動物の組織リモデリングに働く抗原タンパク質と獲得免疫系の分子間相互作用の解明

    2015.4 - 2018.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

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  • 特異的抗原を介した上皮器官形成に関する分子間相互作用の解析系の開発

    2012.4 - 2014.3

    System name:科学研究費助成事業

    Research category:挑戦的萌芽研究

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    Grant type:Competitive

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  • 自己抗原タンパク質を介して組織リモデリングに働く獲得免疫システム

    2011.4 - 2015.3

    System name:科学研究費助成事業

    Research category:基盤研究(B)

    Awarding organization:日本学術振興会

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  • 自己免疫系による脊椎動物の個体形成の解析

    2008.4 - 2010.4

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

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Teaching Experience (researchmap)

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Teaching Experience

  • インターンシップ特別実習b

    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

  • インターンシップ特別実習a

    2022
    Institution name:新潟大学

  • 理学スタディ・スキルズ

    2022
    Institution name:新潟大学

  • 生物学実験

    2021
    Institution name:新潟大学

  • 免疫細胞生物学特論

    2021
    Institution name:新潟大学

  • 免疫細胞生物学

    2020
    Institution name:新潟大学

  • 基礎生命科学セミナー

    2020
    Institution name:新潟大学

  • 生物学特論 IV

    2020
    Institution name:新潟大学

  • 課題研究II(生物学)

    2018
    Institution name:新潟大学

  • 理学スタディ・スキルズ

    2018
    -
    2022
    Institution name:新潟大学

  • 専門力アクティブ・ラーニング

    2018
    Institution name:新潟大学

  • 自然科学基礎実験

    2017
    Institution name:新潟大学

  • 生物学総合演習

    2017
    Institution name:新潟大学

  • 生物学基礎実習a

    2017
    Institution name:新潟大学

  • 課題研究I(生物学)

    2017
    Institution name:新潟大学

  • 生命科学特別セミナーⅡ

    2017
    Institution name:新潟大学

  • 生命科学特別セミナーⅠ

    2017
    Institution name:新潟大学

  • 生物学基礎演習

    2017
    Institution name:新潟大学

  • 生物学-動物A-

    2015
    Institution name:新潟大学

  • 生物英語II

    2014
    Institution name:新潟大学

  • 基礎細胞生物学

    2014
    Institution name:新潟大学

  • 自然科学総論Ⅳ

    2014
    Institution name:新潟大学

  • 生物学実習

    2013
    Institution name:新潟大学

  • 動物生理学I

    2012
    Institution name:新潟大学

  • 生物学-動物A-

    2012
    Institution name:新潟大学

  • 免疫細胞生物学特論

    2012
    -
    2019
    Institution name:新潟大学

  • 日本事情自然系A

    2012
    -
    2017
    Institution name:新潟大学

  • 課題研究I(生物学科)

    2012
    -
    2016
    Institution name:新潟大学

  • 細胞認識学

    2012
    -
    2016
    Institution name:新潟大学

  • 研究発表演習(中間発表)

    2012
    -
    2015
    Institution name:新潟大学

  • 生命・食料科学セミナーBⅠ

    2012
    -
    2015
    Institution name:新潟大学

  • 文献詳読Ⅰ

    2012
    -
    2015
    Institution name:新潟大学

  • 生命・食料科学特定研究BⅡ

    2012
    -
    2015
    Institution name:新潟大学

  • 文献詳読Ⅱ

    2012
    -
    2015
    Institution name:新潟大学

  • 生命・食料科学特定研究BⅠ

    2012
    -
    2015
    Institution name:新潟大学

  • 生命・食料科学セミナーBⅡ

    2012
    -
    2015
    Institution name:新潟大学

  • 基礎生物科学実習I

    2009
    -
    2016
    Institution name:新潟大学

  • 動物形態発生学実習

    2008
    Institution name:新潟大学

  • 発生生物学演習

    2007
    Institution name:新潟大学

  • 生物学実験 I

    2007
    -
    2019
    Institution name:新潟大学

  • 動物生理学実習

    2007
    -
    2016
    Institution name:新潟大学

  • 課題研究II

    2007
    -
    2014
    Institution name:新潟大学

  • 原書講読

    2007
    -
    2012
    Institution name:新潟大学

  • 課題研究I

    2007
    -
    2011
    Institution name:新潟大学

  • 基礎生物科学実習II

    2007
    -
    2008
    Institution name:新潟大学

  • 情報数理生物学実習

    2007
    Institution name:新潟大学

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