A study on the regulatory mechanisms of mammalian early embryogenesis trough the evolutionarily conserved cell polarity regulating system

2013 Fiscal Year Final Research Report

• Project Area: Cell Community in early mammalian development
• Project/Area Number: 21116004
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Yokohama City University
• Principal Investigator: SUZUKI Atsushi 横浜市立大学, 生命医科学研究科, 准教授 (00264606)
• Co-Investigator(Renkei-kenkyūsha): HIROSE Tomonori 横浜市立大学, 医学部, 講師 (20381668) ; NAKAYA Masaaki 横浜市立大学, 医学部, 助教 (70422095)
• Project Period (FY): 2009-07-23 – 2014-03-31
• Keywords: 細胞極性 / 上皮細胞 / 細胞接着 / aPKC / PAR-1 / 微小管 / 細胞運動

Research Abstract

In the very early stages of the mammalian embryogenesis (8 to 32 cells), the establishment of epithelial polarity in the outer cells of the cell mass is crucially important to guarantee the gradual fixation of the fates of the individual cells. Based on the fact that dynamic change of the epithelial cell polarity is crucially important for the mammalian embryonic development, in this research project, we have intensively analyzed the mechanisms by which the evolutionarily-conserved cell polarity-regulating proteins, the PAR-aPKC proteins, control the epithelial polarity. As a result, we succeeded to reveal three kinds of the novel molecular mechanisms, and provided the important insights and basis for the future research on the early embryogenesis of mammals.

Research Products

• [Journal Article] A novel PAR-1-binding protein, MTCL1, plays critical roles in organizing microtubules in polarizing epithelial cells (2013)
  • Author(s): Sato Y, Akitsu M, Amano Y, Yamashita K, Ide M, Shimada K, Yamashita A, Hirano H, Arakawa N, Maki T, Hayashi I, Ohno S, Suzuki A
  • Journal Title: J. Cell Sci. Volume: 126 Pages: 4671-4683
  • DOI: 10.1242/jcs.127845
  • Peer Reviewed
• [Journal Article] Polarity-dependent distribution of angiomotin localizes hippo signaling in preimplantation embryos (2013)
  • Author(s): Hirate Y, Hirahara S, Inoue K, Suzuki A, Alarcon VB, Akimoto K, Hirai T, Hara T, Adachi M, Chida K, Ohno S, Marikawa Y, Sasaki H
  • Journal Title: Curr. Biol. Volume: 23 Pages: 1181-1194
  • DOI: 10.1016/j.cub.2013.05.014
  • Peer Reviewed
• [Journal Article] A novel function of the cell polarity -regulating kinase PAR-1/MARK in dendritic spines (2011)
  • Author(s): Hayashi K, Suzuki A, Ohno S
  • Journal Title: BioArchitecture Volume: 1 Pages: 261-266
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22545177
  • Peer Reviewed
• [Journal Article] Maintenance of dendritic spine morphology by partitioning-defective 1b through regulation of microtubule growth (2011)
  • Author(s): Hayashi K, Suzuki A, Hirai S, Kurihara Y, Hoogenraad CC, Ohno S
  • Journal Title: J. Neurosci. Volume: 31 Pages: 12094-12103
  • DOI: 10.1523/JNEUROSCI.0751-11.2011
  • Peer Reviewed
• [Journal Article] KIBRA suppresses apical exocytosis through inhibition of aPKC kinase activity in epithelial cells (2011)
  • Author(s): Yoshihama Y, Sasaki K, Horikoshi Y, Suzuki A, Ohtsuka T, Hakuno F, Takahashi S, Ohno S, Chida K
  • Journal Title: Curr. Biol. Volume: 21 Pages: 705-711
  • DOI: 10.1016/j.cub.2011.03.029
  • Peer Reviewed
• [Journal Article] ASPP2 Regulates Epithelial Cell Polarity through the PAR Complex (2010)
  • Author(s): Cong, W., Hirose, T., Harita, Y., Yamashita, A., Mizuno, K., Hirano, H., and Ohno, S.
  • Journal Title: Curr.Biol. Volume: 20 Pages: 1408-1414
  • DOI: 10.1016/j.cub.2010.06.024
  • Peer Reviewed
• [Journal Article] The 8th and 9th tandem spectrin-like repeat of utrophin cooperatively form a functional unit to interact with polarity-regulating kinase Par-1b (2010)
  • Author(s): Yamashita K, Suzuki A, Satoh Y. Ide M, Amano Y, Masuda-Hirata M, Hayashi Y, Hamada K, Ogata K, Ohno S
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 391 Pages: 812-817
  • DOI: 10.1016/j.bbrc.2009.11.144
  • Peer Reviewed
• [Presentation] 中心体非依存的な微小管制御を通じた新しい細胞極性制御機構 (2013)
  • Author(s): 鈴木厚、佐藤由典
  • Organizer: 日本細胞生物学会
  • Place of Presentation: 愛知県産業労働センター(愛知県)
  • Year and Date: 2013-06-19
• [Presentation] A novel microtubule binding protein, MARKAP1, cooperates with PAR-1 for the development of the lateral microtubule bundles in epithelial cells. (2012)
  • Author(s): Akitsu M, Satoh Y, Amano K, …, Suzuki A
  • Organizer: 米国細胞生物学会
  • Place of Presentation: サンフランシスコ Moscone Center (米国)
  • Year and Date: 2012-12-18
• [Presentation] Analysis of physiological function of MARKAP1 in the cerebellum (2012)
  • Author(s): Satake T, Hayashi K, Yamashita K, Sato Y, Ohno S, Suzuki A
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡国際会議場 (福岡県)
  • Year and Date: 2012-12-11
• [Presentation] Maintenance of dendritic spine morphology by PAR-1b through regulation of microtubule growth (2011)
  • Author(s): Hayashi K, Suzuki A, Hoogenraad C.C, Ohno S
  • Organizer: 米国細胞生物学会
  • Place of Presentation: デンバー国際会議場 (米国)
  • Year and Date: 2011-12-04
• [Presentation] Hippo経路上流因子KIBRAはaPKC活性を抑制し上皮細胞極性を制御する (2011)
  • Author(s): 吉濱陽平、 …、鈴木厚, 他
  • Organizer: 日本細胞生物学会
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2011-06-28
• [Presentation] 新規PAR-1結合タンパク質 p250は、微小管安定化タンパク質である (2010)
  • Author(s): 鈴木厚ら
  • Organizer: 日本細胞生物学会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-05-20
• [Presentation] Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex (2009)
  • Author(s): Suzuki A. et al.
  • Organizer: 米国細胞生物学会
  • Place of Presentation: サンディエゴ会議センター(米国)
  • Year and Date: 2009-12-09
• [Book] Cell Polarity: Biological Role and Basic Mechanisms (2014)
  • Author(s): Suzuki A
  • Publisher: Springer(in press)
• [Book] 「生体の科学」 63巻3号 (2012)
  • Author(s): 鈴木厚
  • Total Pages: 89-195
  • Publisher: 医学書院
• [Remarks]
  • URL: http://www.tsurumi.yokohama-cu.ac.jp/mcbl/suzuki/index.html