Function and regulation of gap junction on oral epithelium organogenesis

• Project/Area Number: 24390460
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: Tohoku University
• Principal Investigator: Yamada Aya 東北大学, 歯学研究科(研究院), 准教授 (40295085)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA TAKASHI 東北大学, 大学院歯学研究科, 准教授 (90585324) ; SAITO MASAHIRO 東北大学, 大学院歯学研究科, 教授 (40215562) ; SAKAI TAKAYOSHI 大阪大学, 大学院歯学研究科, 教授 (90379082) ; IWAMOTO TSUTOMU 徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授 (90346916)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2012: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 再生医療 / 細胞間結合 / ギャップ結合 / コネキシン４３ / コネキシン43 / 歯髄幹細胞

Outline of Final Research Achievements

Connexin 43 is one of the gap junction protein. To understand the role of connexin 43 (Cx43) in salivary gland development, first we examined the expression of Cx43 by immunostaining using their specific antibody. Cx43 expressed terminal bud epithelum of salivary gland, but not in mesenchymal tisuue. In Cx43 knockout mice, branching morphogenesis of submandibular gland was dramatically inhibited. In presence of inhibitory peptide for Cx43 function, branching morphogenesis of salivary gland organ culture was also inhibited as similar to Cx43 knockout mice. From our results, Cx43 is necessary for salivary gland development and terminal bud branching. Further, gap junctional communication is important for the determination of cell fate. These information is useful for understanding the molecular mechanism of salivary gland development and regeneration.

Research Products

• [Int'l Joint Research] 北京大学(中国)
• [Int'l Joint Research] 米国国立衛生研究所(米国)
• [Journal Article] Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation (2016)
  • Author(s): Liu J, Saito K*, Maruya Y, Nakamura T, Yamada A, Fukumoto E, Ishikawa M, Iwamoto T, Miyazaki K, Yoshizaki K, Ge L, Fukumoto S
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 23670-23670
  • DOI: 10.1038/srep23670
  • NAID: 120006534957
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plakophilin-1, a novel Wnt signaling regulator, is critical for tooth development and ameloblast differentiation (2016)
  • Author(s): Miyazaki K, Yoshizaki K, Arai C, Yamada A, Saito K, Ishikawa M, Xue H, Funada K, Haruyama N, Yamada Y, Fukumoto S, Takahashi I
  • Journal Title: Plos One Volume: 11 Issue: 3 Pages: 0152206-0152206
  • DOI: 10.1371/journal.pone.0152206
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Connexin 43 is necessary for salivary gland branching morphogenesis and FGF10-induced ERK1/2 phosphorylation (2016)
  • Author(s): Yamada A, Futagi M, Fukumoto E, Saito K, Yoshizaki K, Ishikawa M, Arakaki M, Hino R, Sugawara Y, Ishikawa M, Naruse M, Miyazaki K, Nakamura T, Fukumoto S.
  • Journal Title: The Journal of Biological Chemistry Volume: 291 Issue: 2 Pages: 904-912
  • DOI: 10.1074/jbc.m115.674663
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of ex vivo mucocele model using salivary gland organ culture. (2014)
  • Author(s): Hino, R., Futagi, M., Yamada, A., Arakaki, M., Saito, K., Sugawara, Y., Ono, M., Fukumoto, E., Nakamura, T., and Fukumoto, S.
  • Journal Title: Pediatric dental journal Volume: 24(2) Issue: 2 Pages: 78-82
  • DOI: 10.1016/j.pdj.2014.03.003
  • Peer Reviewed / Open Access
• [Journal Article] New insights into the functions of enamel matrices in calcified tissues (2014)
  • Author(s): Fukumoto S, Nakamura T, Yamada A, Arakaki M, Saito K, Xu J, Fukumoto E, Yamada Y.
  • Journal Title: Japanese Dental Science Review Volume: 50-2 Issue: 2 Pages: 47-54
  • DOI: 10.1016/j.jdsr.2014.01.001
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of ex vivo mucocele model using salivary gland organ culture (2014)
  • Author(s): Hino Ryoko, Futagi Masaharu, Yamada Aya , Arakaki Makiko, Saito Kan, Sugawara Yu, Ono Mariko, Fukumoto E, Nakamura T, Fukumoto Satoshi
  • Journal Title: Pediatric Dental Journal Volume: in press
  • Peer Reviewed
• [Journal Article] Differentiation of induced pluripotent stem cells into dental mesenchymal cells (2011)
  • Author(s): Otsu, K., et al
  • Journal Title: Stem Cells Dev. Volume: (e-Pub) Issue: 7 Pages: 1156-1164
  • DOI: 10.1089/scd.2011.0210
  • Peer Reviewed
• [Presentation] Induced artificial bone marrow cells from dental pulp cells of primary tooth using a natural compound (2015)
  • Author(s): Aya Yamada, Takashi Nakamura, Makiko Arakaki, Yu Sugawara, Kan Saito, Satoshi Fukumoto
  • Organizer: 25th Congress of the International Association of Paediatric Dentistry
  • Place of Presentation: Glasgow, Scotland
  • Year and Date: 2015-07-01
  • Int'l Joint Research
• [Presentation] Cross-talk between PDGF-BB and BMP-2 is important for the stemness of dental pulp stem cells (2015)
  • Author(s): Yu Sugawara, Aya Yamada, Satoshi Fukumoto
  • Organizer: 25th Congress of the International Association of Paediatric Dentistry
  • Place of Presentation: Glasgow, Scotland
  • Year and Date: 2015-07-01
  • Int'l Joint Research
• [Presentation] Establishment of ex vivo mucocele model using salivary gland organ culture (2014)
  • Author(s): Ryoko Hino, Masaharu Futagi, Aya Yamada, Makiko Arakaki, Kan Saito, Yu Sugawara, Mariko Ono, Emiko Fukumoto, Takashi Nakamura, Satoshi Fukumoto
  • Organizer: 9th BIENNIAL CONFERENCE OF THE PEDIATRIC DENTISTRY ASSOCIATION OF ASIA
  • Place of Presentation: Singapore
  • Year and Date: 2014-08-23 – 2014-08-24
• [Presentation] Mst1/2 regulate dental epithelium proliferation and ameloblast differentiation (2014)
  • Author(s): Masaharu Futagi, Kan Saito, Takashi Nakamura, Aya Yamada, Satoshi Fukumoto
  • Organizer: 92nd International Association for Dental Research
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2014-06-25 – 2014-06-28
• [Presentation] Novel Compounds Mimic Hedgehog Activity and Promote Osteoblast Differentiation in C3H10T1/2 Cells and Osteoblastic Cells from Runx2-Deficient Mice (2013)
  • Author(s): Nakamura Takashi, Naruse Masahiro, Ikeuchi Tomoko, Komori Toshihisa, Yamada Aya, Iwamoto Masahiro, Fukumoto Satoshi
  • Organizer: American Society for Bone and Mineral Research
  • Place of Presentation: Baltimore,USA
• [Presentation] NGF induces cell proliferation in dental epithelial cells via p75 (2013)
  • Author(s): Ono Mariko, Iwamoto Tsutomu, Arakaki Makiko, Sugawara Yu, Yamada Aya, Saito Kan, Nakamura Takashi, Fukumoto Satoshi
  • Organizer: 2nd Meeting of the International Association for Dental Research-Asia Pacific Region
  • Place of Presentation: Bangkok,Thailand
• [Presentation] 乳歯歯髄を用いた再生医療における課題について (2012)
  • Author(s): 二木かおり,山田亜矢,新垣真紀子,岩本 勉,中村卓史,福本 敏
  • Organizer: 第31回日本小児歯科学会中部地方会大会
  • Place of Presentation: 金沢
  • Year and Date: 2012-11-25
• [Presentation] Connexin43 regulates TGF-SS-induced ERK1/2 signaling in amelogenesis associated with oculodentodigital dysplasia (2012)
  • Author(s): Yamada Aya, Fukumoto Satoshi
  • Organizer: 8^<th> Biennial Conference, Pediatric Dentistry Association of ASIA
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2012-05-26
• [Presentation] Filamin-A regulates dental epithelial cell migration in tooth anomaly associated with Mernick-Needles syndrome (2012)
  • Author(s): Miyamoto Ryoko, Yamada Aya, Fukumoto Satoshi
  • Organizer: 8^<th> Biennial Conference, Pediatric Dentistry Association of ASIA
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2012-05-26
• [Presentation] Pannexin 3, a gap junction protein, regulates odontoblast differentiation (2012)
  • Author(s): Iwamoto Tsutomu, Ishikawa Masaki, Yoshizaki Keigo, Yamada Aya, Nakamura Takashi, Yamada Yoshihiko, Fukumoto Satoshi
  • Organizer: The ^<th> General Session & Exhibition of the IADR
  • Place of Presentation: Iguacu Falls, Brazil
• [Presentation] ラミニン分子を利用した歯原性上皮細胞の増殖―分化制御
  • Author(s): 及川知子，二木正晴，山田亜矢，新垣真紀子，宮本綾子，齋藤 幹，中村卓史，福本 敏
  • Organizer: 第51回日本小児歯科学会大会
  • Place of Presentation: 岐阜
• [Presentation] 新規エナメル芽細胞マーカーSox21における歯胚分化に対する影響
  • Author(s): 齋藤 幹，山田亜矢，中村卓史，福本 敏
  • Organizer: 第51回日本小児歯科学会大会
  • Place of Presentation: 岐阜
• [Presentation] 唾液腺発生過程におけるConnexin43-FGF10 シグナルの解析
  • Author(s): 福本 敏，二木正晴，岩本 勉，中村卓史，山田亜矢
  • Organizer: 第51回日本小児歯科学会大会
  • Place of Presentation: 岐阜