The principle structure of epithelial tubules in tissues is regulated by cellular polarization and depolarization. Epithelial tubules form lumen by establishing apical-basal polarization and extend their surface by branching morphogenesis. Although understanding of cellular functions at the molecular level has been deepened, the molecular mechanism of the formation of epithelial tubules remains to be clarified. In this study, we try to clarify the mechanism how epithelial tubules are formed by humoral factors and extracellular matrix-mediated cell adhesion in the context of cellular polarization. Although there is diversity among tissues in the function and structure, we would like to identify the common and different mechanism in epithelial tubule formation from various tissues by focusing on collective cell elongation, branching and polarization.

To accomplish our aim above, we will try to clarify following points;
1) Identify the combination of growth factors and their downstream signaling that efficiently induces epithelial elongation and branching morphogenesis by using a cultured epithelial cell system.
2) Clarify whether collective cell elongation and branching induced by identified growth factors is conserved or not throughout organs by using an organ culture system prepared from embryonic epithelium such as kidney, lung, pancreas, salivary, and mammary glands.
3) Identity the components in extracellular matrix that are important for polarization, elongation and branching morphogenesis to understand crosstalk between ECM and growth factor signaling.

Although researches on the formation of central nervous and blood vascular systems, which also show tubular structures, have been progressing, this groundbreaking study on epithelial tubular systems has just begun. Progress in this new research area would contribute to understanding of functional relationship between epithelial tissues and other tissues. It is also expected to contribute to understanding of the formation of central nervous and blood vessel systems. In addition, research achievement in this project would be useful for establishing regenerative medicine in next generation, which will be performed on the basis of further understanding of tissue conformation, and for developing novel therapeutic agents for diseases, including cancer.