@article{oai:asahi-u.repo.nii.ac.jp:00013703,
 author = {柏俣, 正典 and KASHIMATA, MASANORI},
 issue = {2002-02-20},
 journal = {2002-02-20},
 month = {2002-02-20, 2021-12-04},
 note = {Epithelio-mesenchymal interactions regulate fetal development and differentiation of many organs. The submandibular gland (SMG) of feta mouse is a fruitful model for the study of mechanisms of the epithelio-mesenchymal interactions. The SMG begins development on day 12 gestation of oral epithelium into underiying mesenchyme, and continues to grow by repeated dichotomous branching of the distal ends of this epithelial buds ; this process is called branching morphogenesis. There is considerable evidence that a variety of growth factors and cell adhesion molecules operate during development and differentiation of fetal tissues, including the epidermal growth factor (EGF) and integrins. We have reported that EGF stimulate branching morphogenesis of fetal SMG, and the mRNAs for EGF, transforming growth factor-α (TGF-α) and EGF receptor (EGFR), and their proteins are expressed in the SMG throughout late fetal development. Recently, we showed that the activated EGFR triggers the RAS/MEX/ERK signaling cascade in the fetal SMG, and that there is age-dependent variation in this pathway. An inhibitor (PD98059) for enzymatic activity of MEK significantly inhibit the branching morphogenesis. There results imply that the ERK signaling is responsible, at least in a part, for the stimulatory effect of EGF on branching morphogenesis of fetal mouse SMG. Moreover, we have also confirmed that other signaling pathways through some specific enzymes such as phospholipase Cγ1, phosphatidylinositol 3-kinase, protein kinase C (PKC) and protein kinase B/Akt are expressed in developing fetal SMG. Many studies have demonstrated that the epithelial branching depends both on the mesenchyme and the epithelial basement membrane. Such epithelio-mesenchymal interactions most probably involve interaction of integrins with their ligands in the extracellular matrix. We also reported that a monoclonal antibody against α6 integrin subunit significantly inhibit the branching morphogenesis, and EGF stimulates synthesis of integrin α6 subunit in developmental SMG. These finding suggested that the function of EGF system to stimulate branching morphogenesis regulates, in a part, expression of α6 integrin subunit by the epithelial cells of the gland rudiment. Since both integrin (α6 subunit) and growth factor (EGF) support the gland development (branching morphogenesis), further study is necessary to analyze, in detail, the signaling cascades and their cross-talking systems stimulated by both membrane receptors for understanding the mechanisms of normal organogenesis and epithelio-mesenchymal interactions.},
 pages = {2002-02-20--2002-02-20},
 title = {顎下腺形態形成における上皮-間葉相互作用の分子メカニズム},
 volume = {2002-02-20},
 year = {}
}