研究テーマ

個体の生と死を越えて
命をつないでいく
生殖細胞の謎にせまる

高等動物は個体としての死を免れる事は出来ないが、有性生殖によって次世代を生み出し、種を存続させる。すなわち、種の存続という観点では、個体は単に次世代に受けつがれる遺伝情報の乗り物にしかすぎず、次世代を生み出す生殖細胞がもっとも重要な細胞種である。ショウジョウバエは、卵巣と精巣にそれぞれ雌性もしくは雄性生殖幹細胞をニッチと呼ばれる微小環境に維持しており、それらが活発に生殖細胞を生み出している。この幹細胞の維持機構、幹細胞から分化した生殖細胞がそれぞれ卵子と精子に成熟して行く機構、および piRNA と呼ばれる生殖巣に特異的に発現している小分子 RNA を含む非コード RNA によるゲノムの安定化機構の解明を目指している。

ヌアージュに局在する Tudor ドメイン蛋白質の一つ、Tejas(TDRD5 fly homolog)(赤)。核内での piRNA 産生にも関与する Piwi 蛋白質(緑)とともに示す。細胞質で piRNA の増幅に機能する Tejas は、哺育細胞の核膜上、細胞質側にドット上に偏在する。

ヌアージュに局在する Tudor ドメイン蛋白質の一つ、Tejas(TDRD5 fly homolog)(赤)。核内での piRNA 産生にも関与する Piwi 蛋白質(緑)とともに示す。細胞質で piRNA の増幅に機能する Tejas は、哺育細胞の核膜上、細胞質側にドット上に偏在する。

バーチャル甲斐ラボツアー

発表論文

Research articles

  • Lin Y, Suyama R, Kawaguchi S, Iki T, Kai T. (2023) Tejas functions as a core component in nuage assembly and precursor processing in Drosophila piRNA biogenesis. J. Cell Biol., 222(10):e202303125
    doi: 10.1083/jcb.202303125
    PubMed ID: 37555815
  • Iki T, Kawaguchi S, Kai T. (2023) miRNA/siRNA-directed pathway to produce noncoding piRNAs from endogenous protein-coding regions ensures Drosophila spermatogenesis. Science Advances, 9(29)
    doi: 10.1126/sciadv.adh0397
  • *Lim L-X, *Isshiki W, Iki T, Kawaguchi S, Kai T. (2022) The Tudor-domain containing protein, Kotsubu (CG9925), localizes to the nuage and functions in piRNA biogenesis in D. melanogaster. Frontiers in Molecular Biosciences (section RNA Networks and Biology), 9:Article 818302
    *Co-first authors
    doi: 10.3389/fmolb.2022.818302
  • *Iki T, Takami M, *Kai T. (2020) Modulation of Ago2 Loading by Cyclophilin 40 Endows a Unique Repertoire of Functional miRNAs during Sperm Maturation in Drosophila. Cell Reports, 33(6):108380--108393
    *Co-corresponding
    doi: 10.1016/j.celrep.2020.108380
  • Kawaguchi S, Ueki M, Kai T. (2020) Drosophila MARF1 ensures proper oocyte maturation by regulating nanos expression. PLoS One, 15(4):e0231114
    doi: 10.1371/journal.pone.0231114
    PubMed ID: 32243476
  • Teo RYW, Anand A, Sridhar V, Okamura K, Kai T. (2018) Heterochromatin protein 1a functions for piRNA biogenesis predominantly from pericentric and telomeric regions in Drosophila. Nat. Commun., 9:1735
    doi: 10.1038/s41467-018-03908-3
  • Quénerch’du E, Anand A, Kai T. (2016) The piRNA pathway is developmentally regulated during spermatogenesis in Drosophila. RNA, 22(7):1044–1054
    doi: 10.1261/rna.055996.116
  • Patil VS, Anand A, Chakrabarti A, Kai T. (2014) The Tudor domain protein Tapas, a homolog of the vertebrate Tdrd7, functions in piRNA pathway to regulate retrotransposons in germline of Drosophila melanogaster. BMC Biol., 12:61
    doi: 10.1186/s12915-014-0061-9
    PubMed ID: 25287931
  • Anand A, Kai T. (2014) Response to ‘Antisense piRNA amplification, but not piRNA production or nuage assembly, requires the Tudor-domain protein Qin’ (Correspondence). EMBO J., 33(6):540–541
    doi: 10.1002/embj.201387548
    PubMed ID: 24652837
  • Lim RSM, Anand A, Nishimiya-Fujisawa C, Kobayashi S, Kai T. (2014) Analysis of Hydra PIWI proteins and piRNAs uncover early evolutionary origins of the piRNA pathway. Dev. Biol., 386(1):237–251
    doi: 10.1016/j.ydbio.2013.12.007
  • Pek JW, Ng BF, Kai T. (2012) Polo-mediated phosphorylation of Maelstrom regulates oocyte determination. Development, 139(24):4505–4513
    doi: 10.1242/dev.082867
  • Anand A, Kai T. (2012) The tudor domain protein Kumo is required to assemble the nuage and to generate germline piRNAs in Drosophila. EMBO J., 31(4):870–882
    doi: 10.1038/emboj.2011.44
  • Pek JW, Kai T. (2011) DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic chromosome segregation. Proc. Natl. Acad. Sci. USA, 108(29):12007–12012
    doi: 10.1073/pnas.1106245108
  • Pek JW, Kai T. (2011) A role for Vasa in regulating mitotic chromosome condensation in Drosophila. Curr. Biol., 21(1):39–44
    doi: 10.1016/j.cub.2010.11.051
  • Patil VS, Kai T. (2010) Repression of retroelements in Drosophila germline via piRNA pathway by the tudor domain protein Tejas. Curr. Biol., 20(8):724–730
    doi: 10.1016/j.cub.2010.02.046
  • Pek JW, Lim AK, Kai T. (2009) Drosophila Maelstrom Ensures Proper Germline Stem Cell Lineage Differentiation by Repressing microRNA-7. Dev. Cell, 17(3):417–424
    doi: 10.1016/j.devcel.2009.07.017
  • Lim AK, Tao L, Kai T. (2009) piRNAs mediate post-transcriptional retroelement silencing and localization to pi-bodies in the Drosophila germline. J. Cell Biol., 186(3):333–342
    doi: 10.1083/jcb.200904063
  • Lim AK, Kai T. (2007) Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA, 104(16):6714–6719
    doi: 10.1073/pnas.0701920104
  • Kai T, Williams D, Spradling AC. (2005) The expression profile of purified Drosophila germline stem cells. Dev. Biol., 283(2):486–502
    doi: 10.1016/j.ydbio.2005.04.018
  • Kai T, Spradling A. (2004) Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries. Nature, 428(6982):564–569
    doi: 10.1038/nature02436
  • Kai T, Spradling A. (2003) An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells. Proc. Natl. Acad. Sci. USA, 100(8):4633–4638
    doi: 10.1073/pnas.0830856100

Review articles

  • Arakawa K, Hirose T, Inada T, Ito T, Kai T, Oyama M, Tomari Y, Yoda T, Nakagawa S. (2023) Nondomain biopolymers: Flexible molecular strategies to acquire biological functions. Genes to Cells,
    doi: 10.1111/gtc.13050
    PubMed ID: 37249032
  • Niwa R, Kai T. (2020) Editorial overview: Stem cells orchestrate oogenesis: a lesson from the fruit fly, Drosophila melanogaster. Curr. Opin. Insect Sci., 37:iii–v
    doi: 10.1016/j.cois.2020.03.001
  • Gleason RJ, Anand A, *Kai T, *Chen X. (2017) Protecting and diversifying the germline. GENETICS, 208(2):435–471
    (A part of FLY BOOK) *Co-corresponding
    doi: 10.1534/genetics.117.300208
  • Lim RSM, Kai T. (2015) A piece of the pi(e): the diverse roles of animal piRNAs and their PIWI partners. Sem. Cell Dev. Biol., 47–48:17–31
    (Special Issue on Coding and Non-coding RNAs)
    doi: 10.1016/j.semcdb.2015.10.025
  • Pek JW, Anand A, Kai T. (2012) Tudor domain proteins in development (Invited Review Article). Development, 139:2255–2266
    doi: 10.1242/dev.073304
  • Pek JW, Patil VS, Kai T. (2012) The piRNA pathway and the potential processing site, the nuage, in the Drosophila germline. Dev. Growth Differ., 54(1):66–77
    doi: 10.1111/j.1440-169X.2011.01316
  • Pek JW, Kai T. (2011) Non-coding RNAs enter mitosis: functions, conservation and implications. Cell Div., 6:6
    doi: 10.1186/1747-1028-6-6
    PubMed ID: 21356070
  • Pek JW, Kai T. (2009) Conserved germline organelle, nuage, serves as site for processing of Piwi-interacting RNAs. (in Japanese). Exp. Med., 27:393–399
  • Kai T. (2004) Germline stem cells and their niches. (in Japanese). Tanpakushitsu Kakusan Koso, 49(6):710–717
  • Spradling A, Drummond-Barbosa D, Kai T. (2001) Stem cells find their niche. Nature, 414(6859):98–104
    doi: 10.1038/35102160

Protocol articles

  • Lim RS, Osato M, Kai T. (2015) Isolation of undifferentiated female germline cells from adult Drosophila ovaries. Curr. Protoc. Stem Cell Biol., 34:2E.3.1–2E.3.14
    doi: 10.1002/9780470151808.sc02e03s22