840 Shijo-cho, Kashihara, Nara 634-8521 JAPAN Public University Corporation NARA MEDICAL UNIVERSITY
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Our research objectives are to understand the cellular mechanisms for animal morphogenesis in the view of cell-cell adhesion system. Cell adhesion molecule cadherins play fundamental roles in physical interaction and selective adhesiveness of cells. Recent studies indicate that the cadherin-based cell adhesion system is involved in the intracellular signals affecting cell shape, cell growth and cell migration. Although it is suggested that some small G proteins and kinases mediate the signals from cell adhesion to these processes, the molecular mechanisms remain to be elucidated. For detail analysis, we isolated mouse teratocarcinoma F9 cells that lack the expression of cadherin-associated protein(s). We have so far isolated alpha-catenin-deficient, beta-catenin-deficient, plakoglobin-deficient and beta-catenin/plakoglobin-deficient cells. These cell lines will be good tools to elucidate the roles of each molecule. We are interested in the roles of cadherin-mediated cell adhesion on four basic mechanisms in animal morphogenesis.

Cytoplasmic regulation of cadherin-mediated cell adhesion.
The involvement of kinases, phosphatases and small G proteins in cadherin-based cell adhesion activity.
Contact regulation of cell growth. 
The effect of cadherin-based cell adhesion on the intracellular signals involved in cell growth.
Contact regulation of cell rearrangement.
The effect of cell-cell adhesion on cell locomotion. Cell migration in confluent cultured cells (intercellular motility).
The roles of cadherin-based cell adhesion on epithelial morphogenesis.
Epithelium formation of F9 cells lacking cadherin-associated protein(s). The role of cadherin-associated proteins in apical membrane formation.
Fig. 1. Morphology of parental F9 cells and beta-catenin/plakoglobin-deficient F9 cells Mouse teratocarcinoma F9 cells express E-cadherin and form closely packed colonies.
Fig. 2. beta-catenin and plakoglobin are indispensable for the function of cadherin cell adhesion molecules. Using gene targeting technology, we isolated beta-catenin/plakoglobin-deficient F9 cells. These cells do not adhere each other and fail to form colonies .
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