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Molecular and developmental biological study on the gut morphogenesis and cytodifferentiation

Research Project

Project/Area Number 11480222
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionTokyo Metropolitan University

Principal Investigator

YASUGI Sadao  Tokyo Metropolitan University, Graduate School of Science Professor, 大学院・理学研究科, 教授 (70011591)

Co-Investigator(Kenkyū-buntansha) FUKUDA Kimiko  Tokyo Metropolitan University, Graduate School of Science Assistant Professor, 大学院・理学研究科, 助手 (40285094)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥5,000,000 (Direct Cost: ¥5,000,000)
Keywordsdigestive tract / morphogenesis / cytodifferentiation / gene expression / chicken embryo / epithelial-mesenchymal interaction / growth factor / transcription factor / 転写制御 / ペプシノゲン / BMP / Notch-Delta / 肺 / DAN / cerberus / Wnt11 / 腱 / 腺上皮 / 内腔上皮 / 側方抑制 / Notch / Delta / Numb / 遺伝子導入 / 胃腺 / 上皮細胞 / ペプシノゲン遺伝子 / Sox / GATA / ゲルシフトアッセー
Research Abstract

The purpose of the present study was to carry out molecular biological, cell biological and experimental embryological research on the morphogenesis and epithelial cytodifferentiation of the digestive organs, necessary for the maintenance of life. In the present work, functional analyses of genes involved in the regionaolization of the digestive tract, genes involved in the morphogenesis of the stomach, growth factors, transcription factors and those related to the epithelial-mesenchymal interactions have been done.
To obtained genes involved in the regionalization, we cloned several genes which showed different expression patterns between the proventriculus (glandular stomach) and gizzard (muscular stomach), and it was shown that their products are important for the differentiation of the mesenchyme. Especially, the differentiation of smooth muscle which is drastically different between the proventriculus and gizzard, we cloned CFKBP/AMP gene related to the smooth muscle differentiation. The mechanism that leads to the formation of smooth muscle layer in the outermost layer of the tract was elucidated with SMAP gene expression as a marker. As for the morphogenesis and cytodifferentiation of the proventriculus, it was revealed that EGF, one of the famous growth factors, and sonic hedgehog produced by epithelial cells play important roles. Also, the specific expression of the embryonic chicken pepsinogen gene in the proventricular gland cells was shown to be regulated by sox and GATA transcription factors. Lastly, we identified BMP2 as an important mesenchymal factor in inducing the proventricular glands and ECPg expression, since its over-expression in the mesenchyme greatly enhances gland formation while over-expression of Noggin, an antagonist of BMP, completely inhibits it. In summary, we could identify many key genes working during the establishment of primitive gut through the formation of functional digestive organs.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] Shimizu, Y.: "Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach"Oncogene. 22. 884-893 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda, J.: "The involvement of signal transduction pathway mediated by epidermal growth factor receptor in the differentiation of chicken glandular stomach"Dev.Growth & Differ.. 44. 501-508 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasugi, E.: "Disruption of mitochondria is an early event during dolichyl monophosphate-induced apoptosis in U937 cells"Zool.Sci.. 19. 7-13 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsushita, S.: "The pre-gut endoderm of chick embryos is regionalized by 1.5 days of development"Dev.Dyn.. 223. 33-47 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakamoto, N.: "Role for cGATA-5 in transcriptional regulation of the embryonic chicken pepsinogen gene by epithelial-mesenchymal interactions in the developing chicken stomach"Dev.Biol.. 223. 103-113 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sukegawa, A.: "The concentric structure of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium"Development. 127. 1971-1980 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Narita, T.: "BMPs are necessary for stomach gland formation in the chicken embryo : A study using virally induced BMP-2 arid Noggin expression"Development. 127. 981-988 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koike, T.: "In vitro analysis of mesenchymal influences on the differentiation of stomach epithelial cells of the chicken embryo"Differentiation. 65. 13-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 八杉貞雄: "よくわかる基礎生命科学"サイエンス社. 149 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu, Y., Yamamichi, N., Saitoh, K., Watanabe, A., Ito, M., Yamamichi-Nishina, M., Mizutani, M., Yahagi, N., Suzuki, T., Sasakawa, C., Yasugi, S., Ichinose, M. and Iba, H.: "Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach"Oncogene. 22. 884-893 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda, J., Tabata, H., Fukuda, K. and Yasugi, S.: "The involvement of signal transduction pathway mediated by epidermal growth factor receptor in the differentiation of chicken glandular stomach"Dev. Growth & Differ.. 44. 501-508 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasugi, E., Uemura, I., Kumagai, T., Nishikawa, Y., Yasugi, S., And You, A.: "Disruption of mitochondria is an early event during dolichyl monophosphate-induced apoptosis in U937 cells"Zool.Sci.. 19. 7-13 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsushita, S., Ishii, Y., Scotting, P.J. and Yasugi, S.: "The pre-gut endoderm of chick embryos is regionalized by 1.5 days of development"Dev.Dyn.. 223. 33-47 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakamoto, N., Fukuda, K., Watanuki, K., Sakai, D., Komano, T., Scotting, P.J. and Yasugi, S.: "Role for cGATA-5 in transcriptional regulation of the embryonic chicken pepsinogen gene by epithelial-mesenchymal interactions in the developing chicken stomach"Dev.Biol.. 223. 103-113 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sukegawa, A., Narita, T., Kameda, T., Saitoh, K., Nohno, T., Iba, H., Yasugi, S. and Fukuda, K.: "The concentric structure of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium"Development. 127. 1971-1980 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Narita, T., Saitoh, K., Kameda, T., Kuroiwa, A., Mizutani, M., Koike, C., Iba, H. and Yasugi, S.: "BMPs are necessary for stomach gland formation in the chicken embryo : A study using virally induced BMP-2 and Noggin expression"Development. 127. 981-988 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koike, T. and Yasugi, S.: "In vitro analysis of mesenchymal influences on the differentiation of stomach epithelial cells of the chicken embryo"Differentiation. 65. 13-25 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasugi, S.: "Basic Life Science"Science-sha. 1-149 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimizu, Y: "Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach"Oncogene. 22. 884-893 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeda, J.: "The involvement of signal transduction pathway mediated by epidermal growth factor receptor in the differentiation of chicken glandular stomach"Dev. Growth a Differ.. 44. 501-508 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasugi, E.: "Disruption of mitochondria is an early event during dolichyl monophosphate-induced apoptosis in U937 cells"Zool. Sci.. 19. 7-13 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsushita, S.: "The pre-gut endoderm of chick embryos is regionalized by 1.5 days of incubation"Dev. Dyn.. 223. 33-47 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 八杉 貞雄: "内胚葉器官の形成とシグナル分子"The Lung Perspectives. 11. 67-73 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 福田 公子: "消化管の分化を制御するBMPとSonic Hedgehog"細胞工学. 21. 471-475 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 八杉 貞雄: "よくわかる基礎生命科学"サイエンス社. 149 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsushita, S. et al.: "Pre-gut endoderm of chick embryo is regionalized by 1.5 days of development"Developmental Dynamics. 223. 33-47 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasugi, E. et al.: "Disruption of mitochondria is an early event during dolichyl phosphate-induced apoptosis in U937 cells"Zoological Science. 19. 7-13 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 八杉貞雄, 松田佳昌: "消化管の形成にかかわる遺伝子"G.I.Research. 9. 197-204 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 西駕秀俊, 八杉貞雄: "たった一つの卵から"東京化学同人. 207 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasugi,S.: "The mesenchymal factors regulating epithelial morphogenesis and differentiation of the chicken stomach"Zoological Science. 17. 1-9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Narita,T.: "BMPs are necessary for stomach gland formation in the chicken embryo : a study using virally induced BMP-2 and Noggin expression"Development. 127. 981-988 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sukegawa,A.: "The concentric structure of the developing gut is regulated by sonic hedgehog derived from endodermal epithelium"Development. 127. 1971-1980 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 八杉貞雄: "消化器官の領域分化における遺伝子カスケード"実験医学. 18(9). 164-170 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 成田知弘: "消化器官形成における上皮-間充織相互作用とBMP"Molecular Medicine. 37(6). 680-685 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakamota,N.: "Role for cGATA-5 in transcriptional regulation of the embryonic chicken pepsinogen gene by epithelial-mesenchymal interactions in the developing chicken stomach"Developmental Biology. 233. 103-113 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasugi,S.: "Gene transfer into chicken embryos as an effective system of analysis in developmental biology"Development, Growth and Differentiation. 42. 195-197 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukuda,K.: "Application of efficient and specific gene transfer systems and organ culture techniques for the elucidation of mechanisms of epithelial-mesenchymal interaction in the developing gut"Development, Growth and Differentiation. 42. 207-211 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 八杉貞雄: "消化管の形態形成遺伝子と疾病"現代医療. 32(8). 95-101 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasugi,S.: "The role of mesenchymal tissue in the development of the gut"Connective Tissue. 32. 273-278 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 福田公子: "消化管形成のボディープラン"現代化学.

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasugi,S.: "Tissue Engineering for Therapeutic Use 4"Elsevier Science B.J.. 9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koike, T.: "Invitro analysis of mesenchymal influences on the differentiation of stomach epithelial cells of chicken embryo"Differentiation. 65. 13-25 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasugi, S.: "The mesenchymal factors regulating epithelial morphogenesis and differentiation of the chicken stomach"Zoological Science. 17. 1-9 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Narita, T.: "BMPs are necessary for stomach gland formation in the chiken embryo:A study using virally induced BMP-2 and Noggin edpression"Development. 127. 981-988 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sukegawa, A.: "the cancentric structure of the developing gut is regulated by sonic hedgeliog derived from endodermal epithelium"Development. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukuda, K.: "Application of the effecient and specitic gene transfer systems and organ culture technique for the elucidation of mechanisms of ejithelial-mesenchymal interaction in tice developing gut."Development, Growth and Differentiation. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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