Mechanisms of a novel Wnt signaling pathway regulating asymmetric division

• Project/Area Number: 19207017
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: SAWA Hitoshi The Institute of Physical and Chemical Research, 構造遺伝学研究センター, 教授 (80222024)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥45,240,000 (Direct Cost: ¥34,800,000、Indirect Cost: ¥10,440,000); Fiscal Year 2010: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2009: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2008: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: 非対称細胞分裂 / Wnt / βカテニン / 紡錘体 / 微小管 / 線虫 / 細胞極性 / 非対称分裂 / C.elegans / 幹細胞 / 非対称細胞 / キナーゼ / C. elegans

Research Abstract

Stem cells divide asymmetrically to produce distinct daughter cells. In the nematode, extracellular signals (Wnts) regulate asymmetric localization of tumor suppressor protein APC on the cell cortex. We discovered that APC regulates asymmetric nuclear localization of β-catenin and distinct gene expression between daughter cells by inducing asymmetry of the spindle structure. Our results show a novel mechanism of signal transduction in which extracellular signals are transmitted into nuclei by modulating microtubules.

Research Products

• [Journal Article] Arata Y., Lee J.Y., Goldstein B., Sawa H. (2010)
  • Author(s): Extracellular control of PAR protein localization during asymmetric cell division in the C. elegans embryo.
  • Journal Title: Development 137 Pages: 3337-3345
  • Peer Reviewed
• [Journal Article] Double bromodomain protein BET-1 and MYST HATs establish and maintain stable cell fates in C.elegans. (2010)
  • Author(s): Shibata Y., Takeshita H., Sasakawa N., Sawa H.
  • Journal Title: Development 137 Pages: 1045-1053
  • Peer Reviewed
• [Journal Article] Regulation of asymmetric positioning of nuclei by Wnt and Src signaling and its roles in POP-1/TCF nuclear asymmetry in C.elegans. (2010)
  • Author(s): Sugioka K., Sawa H.
  • Journal Title: Genes to Cells 15 Pages: 397-407
  • Peer Reviewed
• [Journal Article] Specification of neurons through asymmetric cell divisions. (2010)
  • Author(s): Sawa H.
  • Journal Title: Current Opinion in Neurobiology 20 Pages: 44-49
  • Peer Reviewed
• [Journal Article] Extracellular control of PAR protein localization during asymmetric cell division in the C.elegans embryo. (2010)
  • Author(s): Arata Y., et al.
  • Journal Title: Development Volume: 137 Pages: 3337-3345
  • Peer Reviewed
• [Journal Article] Regulation of asymmetric positioning of nuclei by Wnt and Src signaling and its roles in POP-1/TCF nuclear asymmetry in C. elegans (2010)
  • Author(s): 杉岡賢史, 澤斉
  • Journal Title: Genes to Cells 15 Pages: 397-407
  • Peer Reviewed
• [Journal Article] Double bromodomain protein BET-1 and MYST HATs establish and maintain stable cell fates in C. elegans (2010)
  • Author(s): 柴田幸政, 竹下久子, 笹川典子, 澤斉
  • Journal Title: Development 137 Pages: 1045-1053
  • Peer Reviewed
• [Journal Article] Specification of neurons through asymmetric cell divisions (2010)
  • Author(s): 澤斉
  • Journal Title: Curr Opinion in Neurobiol 20 Pages: 44-49
  • Peer Reviewed
• [Journal Article] Zinovyeva A. Y., Yamamoto Y., Sawa H., Forrester W.C. (2008)
  • Author(s): Complex network of Wnt signaling regulates neuronal migrations during C. elegans development.
  • Journal Title: Genetics 179 Pages: 1357-1371
  • Peer Reviewed
• [Journal Article] β-Catenin asymmetry is regulated by PLA1 and retrograde traffic in C.elegans stem cell divisions. (2008)
  • Author(s): Kanamori T., Inoue T., Sakamoto T., Gengyo-Ando K., Tsujimoto M., Mitani S., Sawa H., Aoki J., Arai H.
  • Journal Title: EMBO Journal 27 Pages: 1647-1657
  • Peer Reviewed
• [Journal Article] Complex network of Wnt signaling regulates neuronal migrations during C.elegans development (2008)
  • Author(s): Zinovyeva AY, 山本優子, 澤斉, Forrester WC
  • Journal Title: Genetics 179 Pages: 1357-1371
  • Peer Reviewed
• [Journal Article] Complex network of Wnt signaling regulates neuronal migrations during C. elegans development (2008)
  • Author(s): Zinovyeva A. Y., Yamamoto Y., Sawa H., Forrester W. C.
  • Journal Title: Genetics 179 Pages: 1357-1371
  • Peer Reviewed
• [Journal Article] β-Catenin asymmetry is regulated by PLA1 and retrograde traffic in C. elegans stem cell divisions (2008)
  • Author(s): Kanamori T., Inoue T., Sakamoto T., Gengyo-Ando K., Tsujimoto M., Mitani S., Sawa H., Aoki J., Arai H.
  • Journal Title: EMBO Journal 27 Pages: 1647-1657
  • Peer Reviewed
• [Journal Article] Two βs or not two βs: regulation of asymmetric division by β-catenin (2007)
  • Author(s): Mizumoto K., Sawa H.
  • Journal Title: Trends in Cell Biology 17 Pages: 465-473
  • Peer Reviewed
• [Journal Article] RMD-1, a novel microtubule-associated protein functions in chromosome segregation in Caenorhabditis elegans. (2007)
  • Author(s): Oishi K., Okano H., Sawa H.
  • Journal Title: Journal of Cell Biology 179 Pages: 1149-1162
  • Peer Reviewed
• [Journal Article] Cyclin E and CDK2 repress the terminal differentiation of quiescent cells after asymmetric division in C.elegans. (2007)
  • Author(s): Fujita M., Takeshita H., Sawa H.
  • Journal Title: PLoS ONE 2
  • Peer Reviewed
• [Journal Article] Cyclin E and CDK2 repress the terminal differentiation of quiescent cells after asymmetric division in C.elegans. (2007)
  • Author(s): Fujita, M
  • Journal Title: PLoS ONE. 2
  • Peer Reviewed
• [Journal Article] Two βs or not two βs:regulation of asymmetric division byβ-catenin (2007)
  • Author(s): Mizumoto, K.
  • Journal Title: Trends in Cell Biology 17 Pages: 465-473
  • Peer Reviewed
• [Journal Article] RMD-1,a novel microtubule-associated protein functions in chromosome segregation in Caenorhabditis elegans (2007)
  • Author(s): Oishi, K
  • Journal Title: Journal of Cell Biology 179 Pages: 1149-1162
  • Peer Reviewed
• [Journal Article] Double bromodomain protein BET-1 and MYST HATs establish and maintain stable cell fates in C.elegans
  • Author(s): Shibata Y.
  • Journal Title: Development (in press)
  • Peer Reviewed
• [Journal Article] Regulation of asymmetric positioning of nuclei by Wnt and Src signaling and its roles in POP-1/TCF nuclear asymmetry in C.elegans
  • Author(s): Sugioka K.
  • Journal Title: Genes to Cells (in press)
  • Peer Reviewed
• [Presentation] A network of multiple Wnts and their receptors synchronizes polarities of epithelial stem cells in C.elegans (2010)
  • Author(s): 澤斉
  • Organizer: European Wnt meeting
  • Place of Presentation: Stockholm
  • Year and Date: 2010-10-29
• [Presentation] Multiple WNTs regulate polarities of seam cells during asymmetric divisions in C.elegans. (2010)
  • Author(s): Yuko Yamamoto, Hisako Takeshita, Hitoshi Sawa
  • Organizer: EMBO Conference Series : C. elegans : Development and Gene Expression June
  • Place of Presentation: Heidelberg. Germany
  • Year and Date: 2010-06-19
• [Presentation] Wntによる非対称分裂制御機構 (2009)
  • Author(s): 澤斉
  • Organizer: 日本生化学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Regulation of asymmetric cell division by Wnt signaling through asymmetric spindle microtubules in C.elegans (2009)
  • Author(s): 澤斉
  • Organizer: 国際発生生物学会(Kenji Sugioka and Hitoshi Sawa)
  • Place of Presentation: エジンバラUK
  • Year and Date: 2009-09-08
• [Presentation] Regulation of Asymmetric Cell Division by Wnt Signaling in C.elegans (2009)
  • Author(s): 澤斉
  • Organizer: CDB Symposium "Shape & Polarity"
  • Place of Presentation: 神戸
• [Presentation] Life without Wnts; Wnt dependent and independent regulation of beta- catenin by Frizzled in cell polarization (2007)
  • Author(s): 澤斉
  • Organizer: Wnt-Signaling in Development and Disease
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2007-09-14
• [Presentation] Life without Wnts:Wnt dependent and independent cell polarization (2007)
  • Author(s): 澤 斉
  • Organizer: Sixteenth International C. elegans Meeting
  • Place of Presentation: Los Angeles,USA
  • Year and Date: 2007-06-28
• [Remarks] ホームページ等
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