A study on novel regulation mechanism to repress precocious meiotic entry in Drosophila male

• Project/Area Number: 15570006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genetics/Genome dynamics
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: INOUE Yoshihiro Kyoto Institute of Technology, Drosophila Genetic Res.Center, Lecturer, ショウジョウバエ遺伝資源センター, 講師 (90201938)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Masamitsu Kyoto Institute of Technology, Dept.of Applied Biology, Professor, 繊維学部, 教授 (00182460)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
• Keywords: Drosophila / male / meiosis / Mitosis / Cyclin / Polo / G2 / M期進行 / LARP / Polo / 染色体凝縮 / Aurora B / LA様タンパク

Research Abstract

The G2 phase just prior to first meiotic division in male is called a growth phase that is an essential period to ensure gene expression required for meiotic divisions and later spermiogenesis in Drosophila. A timing to initiate the first meiotic division is therefore strictly regulated by activity of CDK1. A hypomorphic mutation at the mitotic gene, meteor (mtr) in Drosophila leads to a production of smaller cells in premeiotic cysts consisting of primary spermatocytes. We found that a chromosome condensation has precociously proceeded in the "wee" cells. Another distinctive features in M phase such as nuclear membrane-break-down and formation of spindle-like structure have also already occurred in these "wee" cells within premeiotic cysts. The precocious entry of meiotic divisions did not allow these cells to grow sufficiently. These cytological observations suggest that the mtr gene is involved in a negative regulation to repress initiation of first meiotic division until a completi on of the growth phase in Drosophila males. Surprisingly, these precocious meiotic entry in the mtr males occurred before a sufficient expression of both Cyclin A and Cyclin B. Immunostaining experiments to detect active form of CDK1 indicate that the active MPF has not yet accumulated in cytoplasm of the "wee" cells with precociously condensed chromatin in the mtr males. Consistently, this precocious meiotic entry in mtr was observed even in mutant background of twine gene encoding a Cdc25 orthologue exclusively active before meiotic division. In addition to the precocious meiotic entry, a failure of centrosome separation, spindle abnormality and non-disjunction was also observed during meiotic divisions in the mtr males. The mtr gene corresponds to dlarp that encode a Drosophila ortholog of the LA-related protein sharing a homologous domain with human Lupas Antigen. Our immunostaining experiments localized the Meteor protein to a peripheral region of nucleus at premeiotic stages and to the centrosomes at M phase. We speculate that the Meteor has essential roles in both meiotic entry and meiotic divisions in Drosophila males.

Research Products

• [Journal Article] Drosophila damaged DNA binding protein 1 (D-DDB1) is an essential factor for development. (2005)
  • Author(s): Takata, K., Yoshida, H., Yamaguchi, M., et al.
  • Journal Title: Genetics in press
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mutation in orbit/mast, reveal that the central spindle is comprised of two microtubule populations ; those that initiate cleavage and those that propagate furrow ingression. (2004)
  • Author(s): Inoue Y.H., Savoian, M., Suzuki, T., et al.
  • Journal Title: J.Cell Biol. 166 Pages: 49-60
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic link between p53 and genes required for formation of the zonula adherens junction. (2004)
  • Author(s): Yamaguchi M, Hirose F, Inoue Y.H et al.
  • Journal Title: Cancer Sci. 95 Pages: 436-441
  • NAID: 10013723115
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DREF is required for EGFR signaling during Drosophila wing vein development. (2004)
  • Author(s): Yoshida, H., Kwon, E., Hirose, F., et al.
  • Journal Title: Genes to Cells 9 Pages: 935-944
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic link between p53 and genes required for formation of the zonula adherens junction. (2004)
  • Author(s): Yamaguchi M, Hirose F, Inoue Y.H, Ohno K, Yoshida H, Hayashi Y, Deak P, Matsukage A.
  • Journal Title: Cancer Sci. 95 Pages: 436-441
  • NAID: 10013723115
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Redox regulation of DNA binding activity of DREF in Drosophila. (2004)
  • Author(s): Choi, T.-Y., Park, S.Y., Kang, H.-S., Cheong, J.-H., Kim, H.-D., Lee, B.L., Hirose, F., Yamaguchi, M., Yoo, M.-A.
  • Journal Title: Biochem.J. 378 Pages: 833-838
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transcriptional regulation of the Drosophila caudal homeobox gene by the DRE/DREF system. (2004)
  • Author(s): Choi, Y.-J., Choi, T.-Y., Yamaguchi, M., Matsukage, A., Kim.Y-S., Yoo, M.-A.
  • Journal Title: Nucleic Acids Res. 32 Pages: 3734-3742
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DREF is required for EGFR signaling during Drosophila wing vein development. (2004)
  • Author(s): Yoshida, H., Kwon, E., Hirose, F., Otsuki, K., Yamada, M., Yamaguchi, M.
  • Journal Title: Genes to Cells 9 Pages: 935-944
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Armadillo/Pangolin regulates PCNA and DREF promoter activities. (2004)
  • Author(s): Kwon E., Hayashi, Y.Otsuki, K., Hirose, F., Nishida, Y., Yoo, M.-A., Yamaguchi, M.
  • Journal Title: Biochem.Biophys.Acta. 1679 Pages: 256-262
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Damaged DNA binding protein 1 in Drosophila defense reactions. (2004)
  • Author(s): Takata, K., Shimanouchi, K., Yamaguchi, M., Murakami, S., Ishikawa, G, Takeuchi, R., Kanai, Y., Ruike, T., Nakamura, R., Abe, Y., Sakaguchi, K.
  • Journal Title: Biochem.Biophys.Res.Commun. 323 Pages: 1024-1031
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of dRFX2, a novel RFX family protein in Drosophila. (2004)
  • Author(s): Otsuki, K., Hayashi, Y., Kato, M., Yoshida, H., Yamaguchi, M.
  • Journal Title: Nucleic Acids Res. 32 Pages: 5636-5648
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mutation in orbit/mast, reveal that the central spindle is comprised of two microtubule populations ; those that initiate cleavage and those that propagate furrow ingression. (2004)
  • Author(s): Inoue Y.H., Savoian, M., Suzuki, T., Yamamoto, M., Glover, D.M.
  • Journal Title: J.Cell Biol. 166 Pages: 49-60
• [Journal Article] Genetic Link between p53 and genes required for formation of the zonula adeherens junction. (2004)
  • Author(s): Yamaguchi, M., Hirose, F., Inoue Y.H., Ohno, K., Yoshida, H., Hayashi, Y., Deak, P., Matsukage, A
  • Journal Title: Cancer Sci. 95 Pages: 436-441
• [Journal Article] DREF is required for EGFR signaling during Drosophila wing vein development. (2004)
  • Author(s): Yoshida, H., Kwon, E., Hirose, F., Yamada, M., Yamaguchi, M.
  • Journal Title: Genes to Cells 9 Pages: 935-944
• [Journal Article] Characterization of dRFX2, a novel RFX family protein in Drosophila. (2004)
  • Author(s): Otsuki, K., Hayashi, Y., Yoshida, H., Yamaguchi, M
  • Journal Title: Nucleic Acids Res. 32 Pages: 5636-5648
• [Journal Article] Transcriptional regulation of the Drosophila caudal homeo box gene by the DRE/DREF system. (2004)
  • Author(s): Choi, Y.-J., Choi, T.-Y., Yamaguchi, M., Matsukage, A., Kim.Y.-S., Yoo, M.-A.
  • Journal Title: Nucleic Acids Res. 32 Pages: 3734-3742
• [Journal Article] Drosophila damaged DNA binding protein 1 (D-DDB1) is an essential factctor for development. (2004)
  • Author(s): Takata, K., Yoshida, H., Yamaguchi, M., Sakaguchi, K
  • Journal Title: Genetics 168 Pages: 855-565
• [Journal Article] Spatio-temporal expression of Drosophila mitochondrial transcription factor A during development. (2003)
  • Author(s): Takata, K, Inoue, Y.H., Hirose, F., et al.
  • Journal Title: Cell Biology International 27 Pages: 361-374
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Orbit/Mast, the CLASP orthologue of Drosophila, is required for asymmetric stem cell and cystocyte divisions and development of the polarised microtubule network that interonnects cocyte and nurse cells oogenesis, (2003)
  • Author(s): Mathe, E., Inoue, Y.H., Glover, D.M
  • Journal Title: Development 130 Pages: 901-915
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis. (2003)
  • Author(s): Kwon, E., Seto, H., Hirose, F., et al.
  • Journal Title: Gene 309 Pages: 101-116
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Spatio-temporal expression of Drosophila mitochondrial transcription factor A during development. (2003)
  • Author(s): Takata, K, Inoue, Y.H., Hirose, F., Murakami, S., Shimanouchi, S., Sakimoto, I., Sakaguchi, K.
  • Journal Title: Cell Biology International 27 Pages: 361-374
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Orbit/Mast, the CLASP orthologue of Drosophila, is required for asymmetric stem cell and cystocyte divisions anddevelopment of the polarized microtubule network that interconnects oocyte and nurse cells during oogenesis. (2003)
  • Author(s): Mathe, E., Inoue, Y.H., Palframan, W., Brown, G., Glover, D.M.
  • Journal Title: Development 130 Pages: 901-915
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis. (2003)
  • Author(s): Kwon, E., Seto, H., Hirose, F., Ohshima, N., Takahashi, Y., Nishida, Y., Yamaguchi, M.
  • Journal Title: Gene 309 Pages: 101-116
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila. (2003)
  • Author(s): Nagai, Y., Fujikake, N., Ohno, K., Higashiyama, H., Popiel, H.A., Rahadian, J., Yamaguchi, M., Strittmatter, W.J., Burke, J.R., Toda, T.
  • Journal Title: Hum.Mol.Genet. 12 Pages: 1253-1260
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tandem duplication of alkaline phosphatase genes and polymorphism in the intergenic sequence in Bombyx mori. (2003)
  • Author(s): Itoh, M., Inoue, T., Kanamori, Y., Nishida, S., Yamaguchi, M.
  • Journal Title: Mol.Gen.Genomics 270 Pages: 114-120
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Drosophila damaged DNA binding protein 1(D-DDB1) is an essential factor for development.
  • Author(s): Takata, K., Yoshida, H., Yamaguchi, M., Shimanouchi, K., Murakami, S., Sakaguchi, K.
  • Journal Title: Genetics (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 発生における細胞増殖制御 (2004)
  • Author(s): 山口政光, 加藤容子
• [Book] 遺伝子の転写:ショウジョウバエの形質転換(名取俊二編) (2003)
  • Author(s): 井上喜博, 西田育巧
  • Publisher: 広川書店
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Mathe, E., Inoue, Y.H.: "Orbit/Mast, the CLASP orthologue of Drosophila, is required for asymmetric stem cell and cystocyte divisions and development of the polarised microtubule network that interconnects oocyte and nurse cells during oogenesis"Development. 130. 901-915 (2003)
• [Publications] Kwon, E., Seto, H., Hirose, F., Ohshima, N., Takahashi, Y., et al.: "Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis"Gene. 309. 101-116 (2003)
• [Publications] Takata, K, Inoue, Y.H., Hirose, F., Murakami, S., Shimanouchi, S., Sakimoto, I., et al.: "Spatio-temporal expression of Drosophila mitochondrial transcription factor A during development"Cell Biology International. 27. 361-374 (2003)
• [Publications] Nagai, Y., Fujikake, N., Ohno, K., Higashiyama, H., Popiel, H.A., et al.: "Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila"Hum.Mol.Genet.. 12. 1253-1260 (2003)
• [Publications] Takata, K., Yoshida, H., Yamaguchi, M., Shimanouchi, K., et al.: "Drosophila damaged DNA binding protein 1 (D-DDB1) is an essential factor for development"Genetics. (In press). (2004)
• [Publications] Yamaguchi, M., Hirose, F., Inoue Y.H., Ohno, K., Yoshida, H., et al.: "Genetic Link between p53 and Genes Required for Formation of the Zonula Adeherens Junction"Cancer Sci.. (In press). (2004)
• [Publications] 山口政光, 加藤容子: "増殖関連遺伝子の制御機構.発生における細胞増殖制御(竹内隆・岸本健雄編)"シュプリンガーフェアラーク東京. 198 (2004)