Keishi Otsu
Keishi Otsu, D.D.S., Ph.D.
Division of Developmental Biology & Regenerative Medicine, Department of Anatomy, Iwate Medical University
Our Techniques
We have elucidated key signaling pathways and mechanisms of stem cell maintenance during tooth development. A major strength of our lab is the unique experimental techniques we have established. These include the development of dental cell lines, organ culture of tooth germs, real-time imaging, and the creation of cell type–specific genetically modified mice and fate-mapping models. We also employ micro-CT, electron microscopy, and a variety of molecular and biochemical methods. In recent years, we have integrated GTP metabolism and evolutionary perspectives, along with multi-omics approaches, to achieve a more comprehensive understanding of developmental mechanisms. Building on these findings, we were the first in the world to induce odontoblast differentiation from iPS cells. We are now working to advance this achievement toward full regeneration of teeth and periodontal tissues.

GTP Project

For young researchers
Teeth and bones are organs that emerged during vertebrate evolution. Their formation requires molecular functions that were not present in invertebrates. These functions are also thought to have been acquired during vertebrate evolution. By studying how teeth and bones develop, we seek to reveal how these evolutionarily acquired functions contribute to organ formation. In this project, we focus on PI5P4Kβ, a molecule that gained GTP-sensing ability through evolution. Our goal is to clarify its role in the development of hard tissues, including teeth and bones. We analyze its spatiotemporal expression and use organ culture systems combined with loss-of-function mouse models and pharmacological inhibitors. These approaches allow us to examine the effects of PI5P4Kβ on morphology, metabolism, and signaling. We also perform multi-omics analyses to explore how local GTP metabolism is linked to developmental regulation. Through this, we hope to uncover how the PI5P4Kβ-centered metabolic network is integrated into development and contributes to hard tissue formation. This research will deepen our understanding of molecular evolution and provide a basis for understanding GTP metabolism–related diseases in teeth and bones.