Identification of the molecular target to regulate Cell Polarity during 3 dimensional morphogenesis.

• Project/Area Number: 24590237
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Yokohama City University
• Principal Investigator: Nakaya Masa-aki 横浜市立大学, 医学部, 助教 (70422095)
• Research Collaborator: OHNO Shigeo ; MORIYAMA Kayano ; ASADA Kio ; FUKUDA Ayano
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 細胞極性 / 平面極性 / 形態形成 / 遺伝子相互作用 / aPKC / Daam1 / Wnt-PCP / 発生学 / 形態形成学 / リン酸化プロテオミクス / ノックアウトマウス / 薬剤誘導性遺伝子ノックアウトシステム / 不死化上皮細胞株 / ES細胞株 / プロテオミクス解析 / 発生分化

Outline of Final Research Achievements

Proper regulation of cell polarity and directional cell movements is essential to form correct three-dimensional architecture. Atypical protein kinase C (aPKC) is known as the key regulator for apical-basal (z axis) cell polarity, however, it is not clarified the role in the regulation of cell sheet (x-y plane) polarity, as well as planar cell polarity (PCP) in relation to Wnts and other signaling cascades. In this study, we show that aPKC genetically connect to Daam1 (Dshevelled associated activator of morphogenesis 1), which plays important role in Wnt-PCP signaling. We also found functional interaction between aPKC and Daam1 in Xenopus embryogenesis. Further, we present physical interaction between aPKC and Daam1. These results strongly suggest that aPKC contributes planar cell polarity regulation, in vivo and in vitro.

Research Products

• [Journal Article] Aberrant Expression of the Cell Polarity Regulator aPKCλ/ι is Associated With Disease Progression in Cer (2016)
  • Author(s): Mizushima T, Asai-Sato M, Akimoto K, Nagashima Y, Taguri M, Sasaki K, Nakaya MA, Asano R, Tokinaga A, Kiyono T, Hirahara F, Ohno S, Miyagi E.
  • Journal Title: Int J Gynecol Pathol. Volume: 35 Issue: 2 Pages: 106-17
  • DOI: 10.1097/pgp.0000000000000228
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly. (2015)
  • Author(s): Ajima R, Bisson JA, Helt JC, Nakaya MA, Habas R, Tessarollo L, He X, Morrisey EE, Yamaguchi TP, Cohen ED.
  • Journal Title: Dev Biol. Volume: 408 Issue: 1 Pages: 126-39
  • DOI: 10.1016/j.ydbio.2015.10.003
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 細胞極性及びmRNA監視系を起点とした新規バイオマーカーと創薬標的の開発 (2015)
  • Author(s): 中谷雅明、大野茂男
  • Organizer: 文部科学省「翻訳後修飾プロテオミクス医療研究拠点の形成」・第６回シンポジウム「疾患の克服に向けた翻訳後修飾プロテオミクス医療研究開発」
  • Place of Presentation: 横浜市立大学・福浦キャンパス（神奈川県横浜市）
  • Year and Date: 2015-10-19
• [Presentation] 上皮細胞株の樹立法とその解析 (2014)
  • Author(s): 中谷雅明、森山佳谷乃、浅田希央、井野洋子、平野久、大野茂男
  • Organizer: 新学術「上皮管腔形成」若手主催研究会「In vitro培養系を用いた上皮管腔構造の解析検討会」
  • Place of Presentation: 浜松町センタービル（東京）
  • Year and Date: 2014-11-28
• [Presentation] Identification of Cell Polarity Target Phospho-Protein by Using Inducible Gene Knock-Out Strategy (2013)
  • Author(s): Masa-aki Nakaya
  • Organizer: HUPO 12th Annual World Congress
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] Genetic analysis between single cell polarity gene, atypicalPKC(aPKC), and Dishevelled associated activator of morphogenesis (Daam1), that regulates tissue morphogenesis in cell population. (2013)
  • Author(s): Masa-aki Nakaya
  • Organizer: 新学術領域「哺乳類初期発生の細胞コミュニティー」第6回班会議
  • Place of Presentation: グリーンピア南阿蘇（熊本県阿蘇郡南阿蘇村）
• [Presentation] Identification of Cell Polarity target phospho-protein by using inducible gene knock-out strategy. (2013)
  • Author(s): Masa-aki Nakaya
  • Organizer: The 12th Human Proteome Organisation World Congress (HUPO 2013)
  • Place of Presentation: パフィシコ横浜（神奈川県）
• [Remarks] 横浜市立大学・医学部・分子生物学教室 ホームページ
  • URL: http://www-user.yokohama-cu.ac.jp/~ohnos//Japanease/indexJ.html
• [Patent(Industrial Property Rights)] 子宮頸がんの予防を目的とした前がん病変の進行を予測する検査方法 (2014)
  • Inventor(s): 大野茂男、水島太一、宮城悦子、佐藤美紀子、平原史樹、中谷雅明
  • Industrial Property Rights Holder: 大野茂男、水島太一、宮城悦子、佐藤美紀子、平原史樹、中谷雅明
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-019201
  • Filing Date: 2014-04-01