2002 Fiscal Year Final Research Report Summary
Roles of EGF family molecules during early morphogenetic processes of mouse embryonic submandibular epithelium
Project/Area Number |
13680806
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Developmental biology
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Research Institution | Osaka University |
Principal Investigator |
NAKANISHI Yasuo OSAKA University, graduate school of science, Professor, 大学院・理学研究科, 教授 (40022636)
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Co-Investigator(Kenkyū-buntansha) |
HIEDA Yohki OSAKA University, graduate school of science, Assistant, 大学院・理学研究科, 助手 (30243132)
HIGASHIYAMA Shigeki EHIME University, school of medicine, Professor, 医学部, 教授 (60202272)
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Project Period (FY) |
2001 – 2002
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Keywords | mouse submandibular gland / morphogenesis / epithelial-mesenchymal interactions / EGF family / HB-EGF / neuregulin / collagen gel / male mouse mammary gland |
Research Abstract |
Early morphogenesis of mouse embryonic submandibular gland provides an excellent model for the formation of epithelial lobules as a consequence of epithelial-mesenchymal interactions. We have developed a new hypothesis which emphasizes the mechanical role of mesenchyme in epithelial narrow cleft formation. In that hypothesis, collagen encircling the epithelial lobule is to compress the basal side of the epithelial layer through the contractile activity and flowing movement of mesenchymal cells. The proposed research project was to try to set further evidence on the participation of growth factors of EGF family during morphogenesis of mouse embryonic submandibular gland and mammary gland. The results obtained are as follows; (1) By RT-PCR analysis, HB-EGF, a member of EGF family, was found to be strongly expressed in the submandibular gland. Neuregulin, another member of EGF family, was also expressed and its mouse homolog was successfully cloned. (2) It is of note that neuregulini was found to be expressed in the mesenchyme and the anti-neuregulin antibody significantly inhibited the morphogenesis. (3) Under normal culture condition, colored latex beads (3 micron meter) loaded onto the surface of the mesenchyme invaded deeply into the mesenchyme during culture. 2,3-Butanedione monoxide, an inhibitor of myosin ATPase, however completely inhibited the bead-movement in addition to cleft formation. Interestingly, the inhibitor also inhibited collagen gel contraction by mesenchymal cells. (4) During the morphogenesis of mouse mammary gland, male mammary bud is known to be cut off from the epidermis under the influence of testis androgen. This cleavage was inhibited by an inhibitor of shedding enzymes of EGF family growth factors, suggesting the involvement of EGF family member(s) in this process. (5) The shedding enzymes involved in the formation of soluble EGF family molecules were suggested to be ADAM12.
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Research Products
(12 results)
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[Publications] Umeda, Y., Miyazaki, Y., Shiinoki, H., Higashiyama, S., Nakanishi, Y., Hieda, Y.: "Involvement of heparin-binding EGF-like growth factor and its processing by metalloproteinases in early epithelial morphogenesis of the subandibular gland"Dev. Biol. 237. 202-211 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Asakura, M., Kuakaze, M., Takashima, S., Liao, Y., Ishikura, F., Yoshinaka, T., Ohmoto, H., Node, K., Yoshino, K., Ishiguro, H., Asanuma, H., Sanada, S., Matsumura, Y., Takeda, H., Beppu, S., Tada, M., Hori, M., Higashiyama, S.: "Cardiac hypertrophy is inhibited by antagonism of ADAM 12 processing of HB-EGF : Metalloproteinase inhibitors as a new therapy"Nature Med.. 8. 35-40 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Iwamoto, R., Yamazaki, S., Asakura, M., Takashima, S., Hasuwa, H., Miyako, K., Adachi, S., Kuakaze M., Hashimoto, K., Rabb, G., Klagsbron, M., Narita, D., Hiyashiyama, S., Hori, M., Mekada, E.: "HB-EGF and ErbB signaling is essential for heart function"Proc. Natl. Acad. Sci. U.S.A. (in press). (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Umeda, Y., Miyazaki, Y., Shiinoki, H., Higashiyaoia, S., Nakanishi, Y. and Hieda, Y.: "Inviolvement of heparin-binding EGF-like growth factor and its processing by metalloproteinases in early epithelial morphogenesis of the submandibular gland."Dev. Biol.. 237. 202-211 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Asakura, M., Kitakaze, M., Takashima, S., Lino, Y., Ishikura, F., Yashinaka, T., Ohmoto, H., Node, K., Yoshino, K., Ishiguro, H., Asanuma, H., Sanada, S., Matstunura, Y., Takeda, H., Beppu, S., Tada, M., Hon, M. and Higashiyama, S.: "Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF : Metalloproteinase inhibitors as a new therapy."Nature Med.. 8. 35-40 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Iwaimoto, R., Yamazaki, S., Asakura, M., Takashima, S., Hasuwa, H., Miyado, K., Adachi, S., Kitakaze, M., Hashimoto, K., Rabb, G., Klagsbrun, M., Nanba, D., Higashiyarna, S., Hon, M. and Mekada, E.: "HB-EGF and ErbB signaling is essential for heart function"Proc. Natl, Acad, Sci. U.S.A.. in press. (2003)
Description
「研究成果報告書概要(欧文)」より