| 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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| 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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