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Elucidation of the differentiation mechanism associated with apical-basal polarity determination

Research Project

Project/Area Number 21K19610
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionKyushu University

Principal Investigator

Yoshizaki Keigo  九州大学, 歯学研究院, 助教 (10507982)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords歯 / エナメル芽細胞 / 細胞極性 / 分化 / 上皮細胞 / 極性
Outline of Research at the Start

皮膚などの一般的な上皮組織では、上皮と間葉を隔てる基底膜側に基底側が形成されることから、基底膜が基底側を決定している可能性が考えられるが、歯原性上皮細胞においては、基底膜消失後、頂端側が基底膜側に形成されるという逆転現象が認められる。この結果は、基底膜が消えるという刺激が頂底極性決定に寄与している可能性を示す。本研究では、歯をモデルとした頂底極性決定機構の解析を通して、上皮細胞の極性化機構の解明および極性化因子の同定を図る。

Outline of Final Research Achievements

Teeth are known as organs formed by epithelial-mesenchymal interaction. Enamel, the surface coating of teeth, is the hardest tissue in our body. It is generated by the secretion of enamel matrix by ameloblasts, followed by its extensive mineralization. Ameloblasts are thought to undergo a highly polarized process during differentiation to secrete enamel matrix, however the molecular mechanisms underlying this process remain unclear. This study demonstrates that PKP1, involved in cell adhesion, plays a crucial role in ameloblast polarization by regulating the intracellular localization of ZO-1.

Academic Significance and Societal Importance of the Research Achievements

エナメル質の再生は未だ成し遂げられておらず、現在の歯科治療は欠損したエナメル質を人工物へと置き換えることで行われている。エナメル質再生のためには、細胞の3次元的配置をコントロールする技術が必要と考えられる。本研究によりエナメル芽細胞の極性化機構の一端を解明できたことにより、将来のエナメル質再生技術の一助となる可能性が考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (41 results)

All 2023 2022 2021

All Journal Article (15 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 15 results,  Open Access: 13 results) Presentation (26 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results)

  • [Journal Article] Mediator 1 ablation induces enamel-to-hair lineage conversion in mice through enhancer dynamics.2023

    • Author(s)
      Thaler R, Yoshizaki K, Nguyen T, Fukumoto S, Den Besten P, Bikle DD, Oda Y.
    • Journal Title

      Commun Biol.

      Volume: 6(1) Issue: 1 Pages: 766-766

    • DOI

      10.1038/s42003-023-05105-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Arl4c is involved in tooth germ development through osteoblastic/ameloblastic differentiation2023

    • Author(s)
      Truong Thinh Thi Kim、Fujii Shinsuke、Nagano Ryoko、Hasegawa Kana、Kokura Megumi、Chiba Yuta、Yoshizaki Keigo、Fukumoto Satoshi、Kiyoshima Tamotsu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 679 Pages: 167-174

    • DOI

      10.1016/j.bbrc.2023.09.014

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C-terminus of PIEZO1 governs Ca2+ influx and intracellular ERK1/2 signaling pathway in mechanotransduction2023

    • Author(s)
      Sugimoto Asuna、Iwata Kokoro、Kurogoushi Rika、Tanaka Manami、Nakashima Yumiko、Yamakawa Yoshihito、Oishi Atsushi、Yoshizaki Keigo、Fukumoto Satoshi、Yamamoto Akihito、Ishimaru Naozumi、Iwamoto Tsutomu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 682 Pages: 39-45

    • DOI

      10.1016/j.bbrc.2023.09.080

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Iroquois homeobox 3 regulates odontoblast proliferation and differentiation mediated by Wnt5a expression2023

    • Author(s)
      Narwidina A, Miyazaki A, Iwata K, Kurogoushi R, Sugimoto A, Kudo Y, Kawarabayashi K, Yamakawa Y, Akazawa Y, Kitamura T, Nakagawa H, Yamaguchi-Ueda K, Hasegawa T, Yoshizaki K, Fukumoto S, Yamamoto A, Ishimaru N, Iwasaki T, Iwamoto T.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 650 Pages: 47-54

    • DOI

      10.1016/j.bbrc.2023.02.004

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a novel ex vivo organ culture system to improve preservation methods of regenerative tissues2023

    • Author(s)
      Yuta T, Tian T, Chiba Y, Miyazaki K, Funada K, Mizuta K, Fu Y, Kawahara J, Iwamoto T, Takahashi I, Fukumoto S, Yoshizaki K.
    • Journal Title

      Sci Rep

      Volume: 13(1) Issue: 1 Pages: 3354-3354

    • DOI

      10.1038/s41598-023-29629-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deficiency of G protein‐coupled receptor <i>Gpr111/Adgrf2</i> causes enamel hypomineralization in mice by alteration of the expression of kallikrein‐related peptidase 4 ( <i>Klk4</i> ) during <scp>pH</scp> cycling process2023

    • Author(s)
      Chiba Yuta、Yoshizaki Keigo、Sato Hiroshi、Ikeuchi Tomoko、Rhodes Craig、Chiba Mitsuki、Saito Kan、Nakamura Takashi、Iwamoto Tsutomu、Yamada Aya、Yamada Yoshihiko、Fukumoto Satoshi
    • Journal Title

      The FASEB Journal

      Volume: 37 Issue: 4

    • DOI

      10.1096/fj.202202053r

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of GPI-anchored protein LYPD1 as an essential factor for odontoblast differentiation in tooth development2023

    • Author(s)
      Fu Y, Miyazaki K, Chiba Y, Funada K, Yuta T, Tian T, Mizuta K, Kawahara J, Zhang L, Martin D, Iwamoto T, Takahashi I, Fukumoto S, Yoshizaki K.
    • Journal Title

      J Biol Chem.

      Volume: 299(5) Issue: 5 Pages: 104638-104638

    • DOI

      10.1016/j.jbc.2023.104638

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GSK3beta inhibitor-induced dental mesenchymal stem cells regulate ameloblast differentiation2022

    • Author(s)
      Yamada Aya、Yoshizaki Keigo、Saito Kan、Ishikawa Masaki、Chiba Yuta、Hoshikawa Seira、Chiba Mitsuki、Hino Ryoko、Maruya Yuriko、Sato Hiroshi、Masuda Keiji、Yamaza Haruyoshi、Nakamura Takashi、Iwamoto Tsutomu、Fukumoto Satoshi
    • Journal Title

      Journal of Oral Biosciences

      Volume: 64 Issue: 4 Pages: 400-409

    • DOI

      10.1016/j.job.2022.10.002

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] von Willebrand factor D and EGF domains regulate ameloblast differentiation and enamel formation.2022

    • Author(s)
      Iwata K, Kawarabayashi K, Yoshizaki K, Tian T, Saito K, Sugimoto A, Kurogoushi R, Yamada A, Yamamoto A, Kudo Y, Ishimaru N, Fukumoto S, Iwamoto T.
    • Journal Title

      J Cell Physiol.

      Volume: 237 Issue: 3 Pages: 1964-1979

    • DOI

      10.1002/jcp.30667

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deletion of epithelial cell-specific p130Cas impairs the maturation stage of amelogenesis2022

    • Author(s)
      Inoue Akane、Kiyoshima Tamotsu、Yoshizaki Keigo、Nakatomi Chihiro、Nakatomi Mitsushiro、Ohshima Hayato、Shin Masashi、Gao Jing、Tsuru Kanji、Okabe Koji、Nakamura Ichiro、Honda Hiroaki、Matsuda Miho、Takahashi Ichiro、Jimi Eijiro
    • Journal Title

      Bone

      Volume: 154 Pages: 116210-116210

    • DOI

      10.1016/j.bone.2021.116210

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The tooth-specific basic-helix-loop-helix factor AmeloD promotes differentiation of ameloblasts2022

    • Author(s)
      Jia L, Chiba Y, Saito K, Yoshizaki K, Tian T, Han X, Mizuta K, Chiba M, Wang X, Al Thamin S, Yamada A, Fukumoto S.
    • Journal Title

      Journal of cellular physiology

      Volume: 237(2) Issue: 2 Pages: 1597-1606

    • DOI

      10.1002/jcp.30639

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An ex vivo organ culture screening model revealed that low temperature conditions prevent side effects of anticancer drugs2022

    • Author(s)
      Tian Tian、Miyazaki Kanako、Chiba Yuta、Funada Keita、Yuta Tomomi、Mizuta Kanji、Fu Yao、Kawahara Jumpei、Han Xue、Ando Yuna、Funada Ami、Yamada Aya、Iwamoto Tsutomu、Nakamura Seiji、Takahashi Ichiro、Fukumoto Satoshi、Yoshizaki Keigo
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 3093-3093

    • DOI

      10.1038/s41598-022-06945-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptional regulation of the basic helix-loop-helix factor AmeloD during tooth development2021

    • Author(s)
      Al Thamin S, Chiba Y, Yoshizaki K, Tian T, Jia L, Wang X, Saito K, Li J, Yamada A, Fukumoto S.
    • Journal Title

      Journal of cellular physiology

      Volume: 236(11) Issue: 11 Pages: 7533-7543

    • DOI

      10.1002/jcp.30389

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Connexin 43-mediated gap junction communication regulates ameloblast differentiation via ERK1/2 phosphorylation2021

    • Author(s)
      Yamada A, Yoshizaki K, Ishikawa M, Saito K, Chiba Y, Fukumoto E, Hoshikawa S, Chiba M, Nakamura T, Iwamoto T, Fukumoto S.
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 748574-748574

    • DOI

      10.3389/fphys.2021.748574

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Integration of Single-Cell RNA- and CAGE-seq Reveals Tooth-Enriched Genes2021

    • Author(s)
      Chiba Y.、Yoshizaki K.、Tian T.、Miyazaki K.、Martin D.、Saito K.、Yamada A.、Fukumoto S.、Genomics and Computational Biology Core
    • Journal Title

      Journal of Dental Research

      Volume: - Issue: 5 Pages: 002203452110497-002203452110497

    • DOI

      10.1177/00220345211049785

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] エナメル芽細胞極性化におけるp130Casの機能解析2023

    • Author(s)
      川原 純平, 吉崎 恵悟, 湯田 智美, 井上 茜, 宮崎 佳奈子, 田 甜, 自見 英治郎, 高橋 一郎
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 温度依存性器官培養法を用いた組織長期保存スクリーニングモデルの検討2023

    • Author(s)
      湯田 智美, 吉崎 恵悟, 田 甜, 宮崎 佳奈子, 鮒田 啓太, 水田 敢士, 傅 堯, 川原 純平, 張 玲, 高橋 一郎
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 基底膜分子NephronectinのRGD領域はインテグリンaVb6と結合することでエナメル芽細胞の分化を制御する2023

    • Author(s)
      水田 敢士, 吉崎 恵悟, 湯田 智美, 宮崎 佳奈子, 鮒田 啓太, 田 甜, 傅 堯, 川原 純平, 張 玲, 高橋 一郎
    • Organizer
      第82回日本矯正歯科学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯胚器官培養法を用いた温度制御による組織長期保存スクリーニングモデルの確立2023

    • Author(s)
      湯田 智美, 吉崎 恵悟, 田 甜, 宮崎 佳奈子, 鮒田 啓太, 水田 敢士, 傅 堯, 川原 純平, 張 玲, 高橋 一郎
    • Organizer
      第82回日本矯正歯科学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 川原 純平, 吉崎 恵悟, 湯田 智美, 井上 茜, 宮崎 佳奈子, 田 甜, 韓 涛, 自見 英治郎, 高橋 一郎2023

    • Author(s)
      p130Casはエナメル芽細胞分化過程において細胞極性を制御する
    • Organizer
      第82回日本矯正歯科学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] scRNA-seq解析を用いた新規前象牙芽細胞マーカー遺伝子の同定および機能解析2023

    • Author(s)
      吉崎 恵悟
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Cellular and epigenetic dynamics by which mediator 1 ablation changes cell fate of dental epithelia to that generating hair.2022

    • Author(s)
      Yuko Oda, Keigo Yoshizaki, Roman Thaler, Satoshi Fukumoto, Daniel D. Bikle.
    • Organizer
      ISSCR 2022 Annual Meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] GPIアンカー型タンパク質Lypd1は、前象牙芽細胞特異的に発現し象牙芽細胞分化を制御する2022

    • Author(s)
      傅 堯,宮崎 佳奈子,吉崎 恵悟,千葉 雄太,川原 純平,湯田 智美,田 甜,水田 敢士,福本敏,高橋 一郎
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 歯特異的転写因子AmeloD結合タンパク質の酵母Two-Hybrid法によるスクリーニング2022

    • Author(s)
      岡 桜恵, 佐藤 浩, 千葉 雄太, 吉崎 恵悟, 福本 敏.
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 前象牙芽細胞に特異的に発現するGPIアンカー型タンパク質Lypd1の同定および分化制御機構の解明2022

    • Author(s)
      傅 堯,宮崎 佳奈子,吉崎 恵悟,千葉 雄太,鮒田 啓太,湯田 智美,田 甜,水田 敢士,川原 純平,福本敏,高橋 一郎
    • Organizer
      第45回分子生物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 生体外器官培養システムを用いた温度刺激による長期器官保存法の確立2022

    • Author(s)
      湯田 智美,吉崎 恵悟,田 甜,宮崎 佳奈子,鮒田 啓太,水田 敢士,傅 堯,川原 純平,福本敏,高橋 一郎
    • Organizer
      第45回分子生物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] A basement membrane protein Nephronectin plays important roles in tooth development.2021

    • Author(s)
      Kanji Mizuta, Keigo Yoshizaki, Tomomi Yuta, Kanako Miyazaki, Keita Funada, Tian Tian, Yao Fu, Yuta Chiba, Ichiro Takahashi, Satoshi Fukumoto.
    • Organizer
      A special symposium celebrating the 50th anniversary of the Protein Data Bank
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comprehensive analysis for the gene functions associated with epithelial-mesenchymal interaction in tooth2021

    • Author(s)
      Keigo Yoshizaki
    • Organizer
      SNU KYUSHU joint symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 吉崎 恵悟2021

    • Author(s)
      上皮-間葉ネットワークにおける器官運命決定機構の解明
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 低温器官培養法を用いた抗癌剤シクロホスファミドによる歯胚形成阻害回避モデルの構築2021

    • Author(s)
      田 甜、吉崎 恵悟、宮崎 佳奈子、鮒田 啓太、湯田 智美、水田 敢士、傅 堯、川原 純平、福本 敏、高橋 一郎
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 基底膜分子 Nephronectin は RGD 領域を介してエナメル芽細胞の分化制御に関与する2021

    • Author(s)
      水田 敢士、吉崎 恵悟、宮崎 佳奈子、鮒田 啓太、湯田 智美、田 甜、傅 堯、川原 純平、福本 敏、高橋 一郎
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] デスモゾーム構成因子 Plakophilin 1 は核内移行シグナルを介して細胞増殖を制御する2021

    • Author(s)
      宮崎 佳奈子、吉崎 恵悟、傅 堯、鮒田 啓太、湯田 智美、田 甜、水田 敢士、川原 純平、福本 敏、高橋 一郎
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] GPI アンカー型タンパク質 Lypd1 は象牙芽細胞分化に重要な役割を果たす2021

    • Author(s)
      傅 堯、宮崎佳奈子、吉崎 恵悟、千葉 雄太、鮒田 啓太、田 甜、湯田 智美、水田 敢士、福本 敏、高橋 一郎
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Gタンパク質共役型受容体Gpr111/Adgrf2はエナメル質の石灰化を制御する2021

    • Author(s)
      千葉 雄太、吉崎 恵悟、田 甜、千葉 満生、韓 旭、稲田 幸織、福本 敏
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Comprehensive analysis for the genes associated with epithelial-mesenchymal interactions in tooth2021

    • Author(s)
      Keigo Yoshizaki
    • Organizer
      The 69th Annual meeting of Japanese Association for Dental Research
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 抗がん剤シクロホスファミドの歯胚に与える影響と副作用回避法の検索2021

    • Author(s)
      田 甜、吉崎 恵悟、宮崎 佳奈子、安藤 優那、鮒田 啓太、湯田 智美、水田 敢士、傅 堯、川原 純平、高橋 一郎
    • Organizer
      第80回日本矯正歯科学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] GPIアンカー型タンパク質Lypd1は歯の発生において象牙芽細胞分化を制御する2021

    • Author(s)
      傅 堯、宮崎 佳奈子、吉崎 恵悟、田 甜、鮒田 啓太、湯田 智美、水田 敢士、川原 純平、花田 彩圭、高橋一郎
    • Organizer
      第80回日本矯正歯科学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 基底膜分子Nephronectinは歯の発生においてRGD配列を介してエナメル芽細胞分化を制御している2021

    • Author(s)
      水田 敢士、吉崎 恵悟、宮崎 佳奈子、田 甜、鮒田 啓太、湯田 智美、傅 堯、川原 純平、高橋 一郎
    • Organizer
      第80回日本矯正歯科学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 外胚葉異形成症原因遺伝子Plakophilin 1は転写共役因子として上皮形成を促進する2021

    • Author(s)
      宮崎 佳奈子,吉崎 恵悟,傅 堯,鮒田 啓太,湯田 智美,田 甜,水田 敢士,川原 純平,花田 彩圭,高橋 一郎
    • Organizer
      第80回日本矯正歯科学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] The role of basement membrane protein Nephronectin in tooth development.2021

    • Author(s)
      Kanji Mizuta, Keigo Yoshizaki, Kanako Miyazaki, Keita Funada, Tomomi Yuta, Tian Tian, Yao Fu, Jumpei Kawahara, Ichiro Takahashi
    • Organizer
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  • [Presentation] von Willebrand factor D and EGF domains, a novel extracellular matrix protein, regulates the expression of cadherins in the dental epithelial cells2021

    • Author(s)
      岩田 こころ、河原林 啓太、吉崎 恵悟、杉本 明日菜、福本 敏、岩本 勉
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Published: 2021-07-13   Modified: 2025-01-30  

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