Updated on 2024/10/10

写真a

 
KIKUCHI Mariko
 
Organization
Graduate School of Science Assistant Professor
Graduate School
Graduate School of Science
Undergraduate School
School of Science Department of Biological Science
Title
Assistant Professor
External link

Degree 1

  1. 博士（理学） （ 2019.3   名古屋大学 ） 

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Research Interests 5

  1. Oogenesis

  2. sex determination

  3. Meiosis

  4. germ cell

  5. medaka

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Research Areas 1

  1. Life Science / Developmental biology  / Reproductive Biology

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Research History 1

  1. Nagoya University   Assistant Professor

    2019.4

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    Country：Japan

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Education 2

  1. The Graduate University for Advanced Studies

    2013.4 - 2016.3

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    Country： Japan

  2. Hokkaido University

    2009.4 - 2013.3

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    Country： Japan

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Awards 1

  1. Inoue Research Award for Young Scientists

    2022.2   Inoue Foundation for Science   Identification of germ cell-intrinsic mechanism of sex determination in medaka.

    Mariko Kikuchi

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Papers 7

  1. foxl3, a sexual switch in germ cells, initiates two independent molecular pathways for commitment to oogenesis in medaka Reviewed

    Kikuchi Mariko, Nishimura Toshiya, Ishishita Satoshi, Matsuda Yoichi, Tanaka Minoru

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   Vol. 117 ( 22 ) page： 12174 - 12181   2020.6

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1073/pnas.1918556117/-/DCSupplemental

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  2. Medaka <i>terb1</i> Mutant Displays Defects of Synaptonemal Complex Formation and Sexual Difference in Gametogenesis

    Kameyama, S; Niwa, T; Kikuchi, M; Tanaka, M

    ZOOLOGICAL SCIENCE   Vol. 41 ( 3 ) page： 314 - 322   2024.6

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    Publisher：Zoological Science  

    Formation of the synaptonemal complex (SC) is a prerequisite for proper recombination and chromosomal segregation during meiotic prophase I. One mechanism that ensures SC formation is chromosomal movement, which is driven by the force derived from cytoskeletal motors. Here, we report the phenotype of medaka mutants lacking the telomere repeat binding bouquet formation protein 1 (TERB1), which, in combination with the SUN/KASH protein, mediates chromosomal movement by connecting telomeres and cytoskeletal motors. Mutations in the terb1 gene exhibit defects in SC formation in medaka. Although SC formation was initiated, as seen by the punctate lateral elements and fragmented transverse filaments, it was not completed in the terb1 mutant meiocytes. The mutant phenotype further revealed that the introduction of double strand breaks was independent of synapsis completion. In association with these phenotypes, meiocytes in both the ovaries and testes exhibited an aberrant arrangement of homologous chromosomes. Interestingly, although oogenesis halted at the zygotene-like stage in terb1 mutant, testes continued to produce sperm-like cells with aberrant DNA content. This indicates that the mechanism of meiotic checkpoint is sexually different in medaka, similar to the mammalian checkpoint in which oogenesis proceeds while spermatogenesis is arrested. Moreover, our results suggest that spermatogenesis is mechanistically dissociable from meiosis.

    DOI： 10.2108/zs230108

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  3. Sexually dimorphic dynamics of the microtubule network in medaka (Oryzias latipes) germ cells Reviewed

    Mariko Kikuchi, Miyo Yoshimoto, Tokiro Ishikawa, Yuto Kanda, Kazutoshi Mori, Toshiya Nishimura, Minoru Tanaka

    Development   Vol. 151 ( 5 )   2024.3

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1242/dev.201840

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  4. Functional Modules in Gametogenesis Invited Reviewed International journal

    Mariko Kikuchi, Minoru Tanaka

    Frontiers in Cell and Developmental Biology   Vol. 10   page： 914570 - 914570   2022.5

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

    Gametogenesis, the production of eggs and sperm, is a fundamental process in sexually reproducing animals. Following gametogenesis commitment and sexual fate decision, germ cells undergo several developmental processes to halve their genomic size and acquire sex-specific characteristics of gametes, including cellular size, motility, and cell polarity. However, it remains unclear how different gametogenesis processes are initially integrated. With the advantages of the teleost fish medaka (Oryzias latipes), in which germline stem cells continuously produce eggs and sperm in mature gonads and a sexual switch gene in germ cells is identified, we found that distinct pathways initiate gametogenesis cooperatively after commitment to gametogenesis. This evokes the concept of functional modules, in which functionally interlocked genes are grouped to yield distinct gamete characteristics. The various combinations of modules may allow us to explain the evolution of diverse reproductive systems, such as parthenogenesis and hermaphroditism.

    DOI： 10.3389/fcell.2022.914570

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  5. Increase of cortisol levels after temperature stress activates dmrt1a causing female-to-male sex reversal and reduced germ cell number in medaka. Reviewed International coauthorship

    Adolfi MC, Fischer P, Herpin A, Regensburger M, Kikuchi M, Tanaka M, Schartl M

    Molecular reproduction and development   Vol. 86 ( 10 ) page： 1405 - 1417   2019.10

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

    DOI： 10.1002/mrd.23177

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  6. Novel components of germline sex determination acting downstream of foxl3 in medaka. Reviewed International coauthorship

    Kikuchi M, Nishimura T, Saito D, Shigenobu S, Takada R, Gutierrez-Triana JA, Cerdán JLM, Takada S, Wittbrodt J, Suyama M, Tanaka M

    Developmental biology   Vol. 445 ( 1 ) page： 80 - 89   2019.1

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.ydbio.2018.10.019

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  7. Germ cells in the teleost fish medaka have an inherent feminizing effect Reviewed International coauthorship

    Toshiya Nishimura, Kazuki Yamada, Chika Fujimori, Mariko Kikuchi, Toshihiro Kawasaki, Kellee R. Siegfried, Noriyoshi Sakai, Minoru Tanaka

    PLoS Genetics   Vol. 14 ( 3 ) page： e1007259   2018.3

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science  

    Germ cells give rise to eggs or sperm. However, recent analyses in medaka (Oryzias latipes) showed that germ cells are also important for feminization of gonads, although this novel role of germ cells has not been characterized in detail. Here, we show that the feminizing effect is inherent to germ cells and is not affected by gametogenic stages or the sexual fate of germ cells. Three medaka mutants were generated to demonstrate this effect: figlα mutants, in which follicle formation is disrupted
    meioC mutants, in which germ cells are unable to commit to gametogenesis and meiosis
    and dazl mutants, in which germ cells do not develop into gonocytes. All these different stages of germ cells in XX mutants have an ability to feminize the gonads, resulting in the formation of gonads with ovarian structures. In addition to normal ovarian development, we also suggest that the increased number of gonocytes is sufficient for male to female sex reversal in XY medaka. These results may genetically demonstrate that the mechanism underlying the feminizing effect of germ cells is activated before the sexual fate decision of germ cells and meiosis, probably by the time of gonocyte formation in medaka. Author summary: Germ cells are the only cells that can transfer genetic materials to the next generation via the sperm or egg. However, recent analyses in teleosts revealed another essential role of germ cells: feminizing the gonads. In our study, medaka mutants in which gametogenesis was blocked at specific stages provides the novel view that the feminizing effect of germ cells occurs in parallel with other reproductive elements, such as meiosis, the sexual fate decision of germ cells, and gametogenesis. Germ cells in medaka may have a potential to feminize gonads at the moment they have developed.

    DOI： 10.1371/journal.pgen.1007259

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Books 1

  1. The spectrum of sex

    （ Role： Contributor ,  Molecular mechanisms underlying sexual bipotentiality）

    2024.1 

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Presentations 13

  1. メダカを用いた減数分裂の性差研究 Invited

    菊地真理子

    第492回 発生研セミナー  2024.3.19  熊本大学 発生医学研究所

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    Event date： 2024.3

    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

    Venue：オンライン   Country：Japan  

  2. 有性生殖の多様化を可能とする、配偶子形成のモジュール構造 Invited

    菊地真理子

    第4回 有性生殖研究会  2024.3.8  有性生殖研究会

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    Event date： 2024.3

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Venue：東京大学 弥生キャンパス   Country：Japan  

  3. Sexually dimorphic contributions of REC8 paralogs to meiotic chromosome axis formation in medaka. Invited

    2024 NIG Symposium "Meiosis and Fish"  2023.12.12  国立遺伝学研究所

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    Event date： 2023.12

    Language：English   Presentation type：Oral presentation (invited, special)  

    Venue：国立遺伝学研究所   Country：Japan  

  4. Sexually dimorphic contributions of REC8 paralogs to meiotic chromosome axis formation in medaka. Invited International conference

    M Kikuchi, S Kameyama, K Kamei, R Shimada, K Ishigura, M Tanaka

    2023.12.8 

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    Event date： 2023.12

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Country：Japan  

  5. Dynamic changes of microtubule network during germline sex differentiation. International conference

    M Kikuchi, M Tsuda, Kizuku Kamei, and M Tanaka

    9th International Symposium on the Biology of Vertebrate Sex Determination 2023  2023.4.19  Vertebrate Sex Determination Organizing Committee

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    Event date： 2023.4

    Language：English   Presentation type：Poster presentation  

    Venue：Kailua-Kona, Hawaii   Country：United States  

  6. メダカ生殖細胞におけるオーキシン依存的ノックダウン法（AID法）の有用性

    菊地真理子、Nadia Eliora、西村浩平、田中実

    第45回 日本分子生物学会年会  2022.12.2  日本分子生物学会

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    Event date： 2022.11 - 2022.12

    Language：Japanese   Presentation type：Poster presentation  

    Venue：千葉県千葉市 幕張メッセ   Country：Japan  

  7. The sexual difference in meiosis Invited International conference

    M Kikuchi and M Tanaka

    1st Annual Symposium on Meiotic Chromosome Dynamics in Zebrafish  2022.9.14 

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    Event date： 2022.9

    Language：English   Presentation type：Oral presentation (invited, special)  

  8. Functional Modules in Gametogenesis

    M Kikuchi and M Tanaka

    55th Annual Meeting of the Japanese Society of Developmental Biologists  2022.6.2 

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    Event date： 2022.5 - 2022.6

    Language：English   Presentation type：Oral presentation (general)  

    Country：Japan  

  9. 染色体の構造と動態からみた減数分裂の性差 Invited

    菊地真理子

    2022年度 遺伝研研究会「有性生殖における染色体・クロマチン・核動態に関する若手研究者の会」  2022.4.14  国立遺伝学研究所

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    Event date： 2022.4

    Language：English   Presentation type：Oral presentation (general)  

    Venue：国立遺伝学研究所   Country：Japan  

  10. Exploring the "meiotic module" using hermaphroditic fish, Amazon molly.

    Mariko Kikuchi

    Retreat in Sugashima "epigenome, meiosis, germ cells"  2023.9.21 

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    Event date： 2023.9

    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

    Country：Japan  

  11. 生殖細胞の性決定機構からみえてきた配偶子形成のモジュール構造 Invited

    菊地真理子

    第4回メダカユーザーヒアリング  2023.6.14  ナショナルバイオリソースNBRPメダカ

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    Event date： 2023.6

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Venue：オンライン   Country：Japan  

  12. 卵を作り出すしくみ:細胞極性をもたらすBalbiani bodyの形成機構 International conference

    菊地真理子、津田弥与、西村俊哉、田中実

    第44回 日本分子生物学会年会  2021.12.2  日本分子生物学会

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    Event date： 2021.12

    Language：Japanese   Presentation type：Poster presentation  

    Venue：神奈川県横浜市   Country：Japan  

  13. 卵形成コミットメントの分子機構 International conference

    菊地真理子、西村俊哉、丹羽大樹、田中実

    第42回 日本分子生物学会年会  2019.12.6  日本分子生物学会

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    Event date： 2019.12

    Language：Japanese   Presentation type：Poster presentation  

    Venue：福岡県福岡市 マリンメッセ福岡   Country：Japan  

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Research Project for Joint Research, Competitive Funding, etc. 6

  1. 雌性発生魚Amazon mollyのscRNA-seqによる生殖様式多様化機構の解明

    Grant number：24NIBB450  2024.4 - 2025.3

    2024年度 基礎生物学研究所 共同利用研究  統合ゲノミクス共同利用研究

    重信秀治

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\46060 （ Direct Cost: \46060 ）

  2. 減数分裂性差の解析

    Grant number：K24-30  2024.4 - 2025.3

    令和6年度 発生医学研究所共同研究 

    石黒啓一郎

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\320000 （ Direct Cost: \320000 ）

  3. 雌性発生魚Amazon mollyのscRNA-seqによる生殖様式多様化機構の解明

    Grant number：23NIBB455  2023.7 - 2024.3

    2023年度 基礎生物学研究所 共同利用研究  統合ゲノミクス共同利用研究

    重信秀治

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\39580 （ Direct Cost: \39580 ）

  4. 減数分裂性差の解析

    Grant number：K23-01  2023.4 - 2024.3

    令和5年度 発生医学研究所共同研究 

    石黒啓一郎

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\800000 （ Direct Cost: \800000 ）

  5. 小型魚類培養系を用いた減数分裂過程のイメージング法の確立

    Grant number：49A2023  2023.4 - 2024.3

    2023年度 国立遺伝学研究所 共同研究NIG-JOINT 

    酒井則良

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    Authorship：Coinvestigator(s) 

    Grant amount：\136000 （ Direct Cost: \136000 ）

  6. 減数分裂性差の解析

    Grant number：K22-03  2022.4 - 2023.3

    令和4年度 発生医学研究所共同研究 

    石黒啓一郎

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    Authorship：Coinvestigator(s)  Grant type：Competitive

    Grant amount：\600000 （ Direct Cost: \600000 ）

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KAKENHI (Grants-in-Aid for Scientific Research) 5

  1. 生殖ライフスパンにおける生殖細胞の性の恒常性維持機構の解明

    Grant number：24H02043  2024.4 - 2026.3

    科学研究費助成事業  学術変革領域研究(A)

    菊地 真理子

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    Authorship：Principal investigator 

    Grant amount：\9360000 （ Direct Cost: \7200000 、 Indirect Cost：\2160000 ）

    本研究は、「生殖細胞の性」という明確な形質に着目して生殖ライフスパンの動的な性質に迫る。そのために、成体期以降のfoxl3変異体において観察される精子形成から卵形成への性転換がどのような階層性（全身・器官・細胞）で制御されているのかを解析するとともに、生殖細胞の性転換をもたらす細胞内分子機構および体細胞からのシグナル伝達経路をRNA-seq解析により探求する。これらの研究により、生殖ライフスパンを「生殖細胞の性の恒常性」という新たな視点で捉えることが目的である。

  2. Live-imaging of meiotic chromosome structures on the absolute time axis

    Grant number：21KK0129  2021.10 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

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    Authorship：Coinvestigator(s) 

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  3. Molecular mechanisms for commitment to oogenesis

    Grant number：21K15133  2021.4 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

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    Authorship：Principal investigator 

    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  4. Underlying mechanism of germline sex determination by FOXL3 and its co-factors

    Grant number：19K23749  2019.8 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    Kikuchi Mariko

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\2860000 （ Direct Cost: \2200000 、 Indirect Cost：\660000 ）

    Using CRISPR/Cas9 system, I generated medaka mutant lines of fbxo47 and rec8a, direct targets of FOXL3. fbxo47-mutant females were sterile, while males were fertile. The mutant ovaries lacked follicles, and chromosome in germ cells exhibited ring-like morphology possibly caused by telomere fusion. Furthermore, the fbxo47-mutant germ cells committed into spermatogenesis, suggesting that FBXO47 has a role in suppression of spermatogenesis. rec8a-mutant females were also sterile, and progression of meiosis was severely defected in germ cells. These results firstly revealed the molecular pathways that initiates several events in female germ cells (e.g. folliculogenesis, suppression of spermatogenesis, and meiosis progression).

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  5. 生殖細胞のオス化機構の解明―精子形成はどのようにして開始されるのか―

    Grant number：16J10351  2016.4 - 2018.3

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    菊地 真理子

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    Authorship：Principal investigator 

    生殖細胞が「精子になるか卵になるか」の運命決定(生殖細胞の性決定)は、有性生殖を行なう生物にとって根本的な問題である。これまで生殖細胞の性は、生殖細胞を取り囲む体細胞の性によって決まると考えられてきた。しかしながら、実際に生殖細胞内で働く分子機構は、脊椎動物では全く明らかになっていない。
    最近我々の研究室では、「生殖細胞自律的な性決定因子」foxl3を同定することに成功した。foxl3の機能を欠損させたメダカ(以下、foxl3-/-)では、遺伝的メス個体の卵巣内に受精可能な精子が作られる。さらに、foxl3-/-の生殖細胞を野生型(以下、WT)個体の卵巣に移植すると、宿主(体細胞)の性に関わらず機能的な精子が形成される。これらのことは、foxl3がメスの生殖細胞内で精子形成の開始を抑制していることを示している。本研究では、転写因子foxl3が制御するターゲット遺伝子の同定を通じて、生殖細胞の自律的な性決定機構を解明することを目的としている。
    平成29年度は、前年度に行った網羅的発現解析で同定されたfoxl3下流変動遺伝子群のスクリーニングに加え、抗FOXL3抗体を用いたChIP-qPCR解析を行い、FOXL3の直接のターゲット遺伝子を同定することに成功した。現在はFOXL3ターゲット遺伝子の変異体作成および表現型解析を進めている。
    上記解析と並行して、iDamIDseq法によるFOXL3結合モチーフの決定をおこなった。その結果、FOXL3結合モチーフはForkhead familyタンパク質のgeneral consensus elementと類似していることが明らかとなった。従ってFOXL3は、ターゲット特異性を決めるために、補因子と相互作用していると考えられる。

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Teaching Experience (Off-campus) 1

  1. Developmental Engineering

    2021.11 （Tokyo University of Science）

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    Level：Undergraduate (specialized)  Country：Japan

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Social Contribution 5

  1. メダカは雌も雄も卵を作る準備をする〜卵の極性を作り出す仕組みを発見〜

    Role(s)：Media coverage

    名古屋大学  名古屋大学オンライン記者会見  2024.3

  2. 生命をつなぐ性と生殖の不思議

    Role(s)：Appearance

    名古屋大学  名大発 アカデミックフラッシュ 第13報  2022.8

  3. 生命をつなぐ性と生殖細胞の不思議

    Role(s)：Lecturer

    名古屋大学  名古屋大学女子中高生理系進学推進セミナー2022  2022.8

  4. 菊地真理子助教 第38回井上研究奨励賞を授賞

    Role(s)：Contribution

    名古屋大学同窓会  名古屋大学同窓会誌  2022.6

  5. 日本発！世界にはばたく研究用生物メダカのはなし

    Role(s)：Lecturer

    名古屋大学  名古屋大学オープンレクチャー2021  2021.3

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Media Coverage 7

  1. メダカは雌も雄も卵を作る準備をする、卵の極性発生の仕組みを名古屋大学などが発見 Internet

    大学ジャーナルオンライン  https://univ-journal.jp/243196/?cn-reloaded=1  2024.3

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    Author：Other 

  2. メダカ初めはみんなメス　名大など発表　確実に子をつくるためか Newspaper, magazine

    中日新聞  朝刊 3面  2024.3

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    Author：Other 

  3. 名大、メダカはメスもオスもまず卵を作る準備をすることを発見 Internet

    マイナビTEC+  https://news.mynavi.jp/techplus/article/20240314-2906200/  2024.3

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  4. メダカは雄も雌も卵を作る準備をする 〜卵の極性を作り出す仕組みを発見〜 Internet

    日本の研究.com  https://research-er.jp/articles/view/131765  2024.3

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  5. 卵だけ作り出す仕組み発見 Newspaper, magazine

    日経産業新聞  6面  2020.7

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    Author：Other 

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  6. 卵を作るメダカのスイッチ 遺伝子が働かないと…メスなのに精子形成も 名大チーム発表 Newspaper, magazine

    朝日新聞  夕刊（名古屋版）7面  2020.5

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  7. メダカのメス、卵を作れる仕組み解明 名古屋大 Internet

    朝日新聞デジタル  https://digital.asahi.com/articles/ASN5P3G63N53OIPE00Y.html  2020.5

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