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Title of Project

Regulation of polarity signaling during morphogenesis, remodeling, and breakdown of epithelial tubular structure
Akira Kikuchi (Osaka University, Graduate School of Medicine, Professor)

Purpose of the Research Project

Epithelial tubular structures are essential units for each organ. Epithelial stem cells differentiate into epithelial cells, which form tubule-like structures through assembly and coherent association, and its structures are maintained. Disruption of epithelial tubular structures leads to developmental malformations and various postnatal diseases, including cancer. While understanding of cellular functions at the molecular level has been deepened, the molecular mechanism of the formation and maintenance of epithelial tubules remains to be clarified.

There are various patterns of epithelial tubular structures, depending on organs. However, we assume that the principle structure of epithelial tubules is regulated by cellular polarization. In this project, we challenge to clarify unresolved issues existed between cell and organ levels: how epithelial cells are polarized to form tubular structures; how disruption of epithelial tubular structures results in diseases.

Content of the Research Project

Understanding of the mechanism underlying the formation of epithelial tubular structures and that of its disruption are two side of the same coin. Therefore, simultaneous analyses of both normal and pathological conditions are required to clarify the molecular mechanism of the formation and maintenance of epithelial tubular structures via cell polarity regulation. Thus, this project has two cooperative research groups with different strategies to clarify the mechanism of “formation and maintenance of epithelial tubular structures” and “disruption of epithelial tubular structures”.

Expected Research Achievements and Scientific Significance

While 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 developing regenerative medicine in next generation, which will be performed on the basis of further understanding of tissue conformation. Finally, we would like to establish new scientific field called “Tubulology (Tubule + biology)” by promoting this new research.