September 3, 2018
Keio University
Amid recent expectations for regenerative medicine, the elucidation of three-dimensional organogenesis mechanisms is considered increasingly important. In particular, while our bodies contain numerous tubular tissues such as the lungs, digestive tract, and blood vessels, the mechanisms by which these tubes are formed are poorly understood. Professor Masaya Imoto and Senior Assistant Professor Koji Hotta of the Faculty of Science and Technology, Keio University, along with Yuji Mizotani (a third-year student in the Doctoral Programs at the university's Graduate School of Science and Technology), addressed this issue. Using sea squirts, which are suitable for tissue observation, they employed chemical biology research methods to discover a compound that inhibits notochord tube formation. Next, they found that this compound binds to a specific protein and inhibits its interaction with another protein. By analyzing the role of this two-protein interaction in notochord tube formation, they revealed that the interaction induces a "flow" of substances from the basal side of the cell toward the lumen, and that various basal factors involved in lumen formation are transported to the lumen by riding this "flow." This is the world's first elucidation of such a mechanism. This research represents a unique approach that integrates chemical biology and developmental biology. In the process, an unexpected link between tube formation and cancer also emerged. This study is expected to provide insights not only in the field of developmental biology but also in a wide range of fields, including regenerative medicine and cancer research.
The research findings were published online in the *Proceedings of the National Academy of Sciences* (PNAS) on August 29, 2018 (U.S. Eastern Time).
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