Signaling systems that respond to cell-cell contact and regulate epithelial polarity

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(Hayashi) To understand the molecular basis for cell motility control during organogenesisi of tubular organs, we have developed an in vivo imaging system of cytosletetal and membrane components and made the following findings.1)In vivo function of the small GTPase RAC was examined. Activation of RAC caused down-regulation of E-cadherin expression and inhibited epithelial cell adhesion and a loss of apical-basal polarity. The results suggests that Rac is primarily involved in maintaining plasticity of epithelia to assure smooth remodeling during morphogenesis.2)Extension of cytoplasmic processes was studied using tracheal terminal branch as a model, and was found that the stereotyped pattem of terminal branch extension correlates with expression of signaling molecules defining positional information in the epidermis. We found that extension of terminal branch is guided by Hedgehog and Dpp that are secreted from the epidermis, thereby correct matching of respiratory system with its targ … More et organ.3)A large scale screening for genes regulating epithelial morphogenesis was performed using a gain of function system. Several novel gene activity controlling cell adhesion, cell motility and guidance were identified.(Nagafuchi) To understand the precise roles of cell-cell adhesion in the establishment of epithelia, the function of cadherin-catenin system was assessed by gene target approach in F9 teratocarcinome cell line.1)F9 cell deficient in alpha-catenin still able to form tight junction. The result suggets that tight junction can form in the absence of cadherin-catenin dependent strong cell-cell adhesion.2)Functions of plakoglobin and beta-catenin were assessed by the gene knockout approach. F9 cells deficient of beta catenin are able to establish nearly complete epithelia. Knockout of plakoglobin caused defects in desmosome formation. Double knockout cells failed to express many of epithelia-specific genes, suggesting essential requirement for those two genes in epithelia formation. The results also suggest that the function of beta catenin can be compensated by plakoglobin. Less