Epithelial- mesenchymal (E-M) interactions play primary roles in development of epithelial organs. Most analyses of mechanisms mediating these E-M interactions have focused on components of the extracellular matrix (ECM). Recent advances in our understanding of cell adhesion molecules now afford an opportunity to examine the role of the actual epithelial cells in these interactions. Integrins constitute a class of cell surface proteins that serve as receptors for specific ECM components. The submandibular gland (SMG) of the fetal mouse presents a well characterized system to study epithelial-mesenchymal interactions both in vivo and in vitro. Published studies and preliminary data of the PI indicate that EGF and TGF alpha promote development of the SMG in culture, while an inhibitor of the EGF receptor (tyrphostin) diminishes SMG growth and development. The investigators hypothesize that these growth factors may be influencing SMG development by regulating expression of integrins on epithelial cells, which subsequently dictates the nature of their interactions with the mesenchyme during development.
Three Specific Aims are proposed to address this hypothesis: 1) To characterize the expression of integrins and ECM components during development of the SMG in vivo and in vitro and to establish if perturbations of these molecules interferes with normal SMG development. 2) To characterize the effects of EGF and TGF alpha on SMG development in vitro and to determine if these growth factors regulate expression of integrins and their ECM ligands. 3) To establish whether EGF and TGF alpha are physiologic regulators of SMG development and to determine whether they are produced by mesenchymal cells of the SMG. Results of these studies are expected to enhance the understanding of SMG developmental dynamics and potentially yield insight into the other processes impacted on by SMG epithelial mesenchymal interactions such as wound healing, metastasis and the genesis of congenital malformations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE010858-04
Application #
2683995
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1995-04-01
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
City College of New York
Department
Anatomy/Cell Biology
Type
Other Domestic Higher Education
DUNS #
603503991
City
New York
State
NY
Country
United States
Zip Code
10031
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Barka, Tibor; Gresik, Edward S; Miyazaki, Yuji (2005) Differentiation of a mouse submandibular gland-derived cell line (SCA) grown on matrigel. Exp Cell Res 308:394-406
Barka, Tibor; Gresik, Edward S; Henderson, Scott C (2004) Production of cell lines secreting TAT fusion proteins. J Histochem Cytochem 52:469-77
Kurabuchi, Shingo; Gresik, Edward W; Hosoi, Kazuo (2004) Additive and/or synergistic action (downregulation) of androgens and thyroid hormones on the cellular distribution and localization of a true tissue kallikrein, mK1, in the mouse submandibular gland. J Histochem Cytochem 52:1437-46
Koyama, Noriko; Kashimata, Masanori; Sakashita, Hideaki et al. (2003) EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland. Dev Dyn 227:216-26
Kurabuchi, Shingo; Hosoi, Kazuo; Gresik, Edward W (2002) Developmental and androgenic regulation of the immunocytochemical distribution of mK1, a true tissue kallikrein, in the granular convoluted tubule of the mouse submandibular gland. J Histochem Cytochem 50:135-45
Kashimata, M W; Sakagami, H W; Gresik, E W (2000) Intracellular signalling cascades activated by the EGF receptor and/or by integrins, with potential relevance for branching morphogenesis of the fetal mouse submandibular gland. Eur J Morphol 38:269-75
Barka, T; Gresik, E W; van Der Noen, H (2000) Transduction of TAT-HA-beta-galactosidase fusion protein into salivary gland-derived cells and organ cultures of the developing gland, and into rat submandibular gland in vivo. J Histochem Cytochem 48:1453-60
Kashimata, M; Sayeed, S; Ka, A et al. (2000) The ERK-1/2 signaling pathway is involved in the stimulation of branching morphogenesis of fetal mouse submandibular glands by EGF. Dev Biol 220:183-96
Kurabuchi, S; Da, J T; Gresik, E W et al. (1999) An unusual sexually dimorphic mosaic distribution of a subset of kallikreins in the granular convoluted tubule of the mouse submandibular gland detected by an antibody with restricted immunoreactivity. Histochem J 31:19-28

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