Laboratory for Histogenetic Dynamics

The development of multicellular organisms involves the collective effect of multiple events at the level of the individual cell, such as proliferation, differentiation, adhesion, and migration. Programmed cell death, for example, is a process by which cells are selected for death at set times in development, allowing for the sculpting of tissue, and is used in the adult organism to maintain homeostasis by eliminating cells that have developed abnormalities. Perturbations in cell death signaling can thus affect an organism’s physiological stability, and result in developmental defects, tumorigenesis, or neurodegenerative disease. Cell death plays an important role in maintaining the cellular society not only by eliminating unneeded cells at given sites and stages, but in other functions, such as regulating the proliferation and migration of neighboring cells, as well. Such cellular behaviors give rise to cell networks capable of organizing into tissues, the study of which requires a experimental approach to spatiotemporal information in living systems, such as can be obtained through the real-time live imaging of biological phenomena. We have chosen the fruit fly Drosophila melanogaster as our primary research model, seeking to take advantage of its utility in developmental studies and wealth of genetic data in studying the coordination of histogenesis through live imaging and genetic screens. Through the use of the extensive Drosophila genetics toolset and live imaging technologies, we hope to be able to address questions that have proven technically challenging in the past, and by visualizing the activities of individual cells, develop a better understanding of how cellular network systems work in histogenesis.

Research Subjects

• Physiological roles and regulating mechanisms of apoptosis during histogenesis
• Dynamics of cellular behaviors which promotes histogenesis
• Cell-to-cell communication which induces histogenesis

Publications

1. Takeishi A, Kuranaga E, Tonoki A, Misaki K, Yonemura S, Kanuka Hirotaka, Miura M.:
   "Homeostatic epithelial renewal in the gut is required to dampen a fatal systemic wound response in Drosophila. "
   Cell Reports, 2013 in press
2. Sekine Y, Hatanaka R, Watanabe T, Sono N, Iemura S, Natsume T, Kuranaga E, Miura M, Takeda K, Ichijo H.:
   "The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5."
   Molecular Cell 48:692-704. 2012
3. Kuranaga E, Matsunuma T, Kanuka H, Takemoto K, Koto A, Kimura K, Miura M.:
   "Apoptosis controls the speed of looping morphogenesis in Drosophila male terminalia."
   Development 138:1493-9. 2011
4. Koto A, Kuranaga E, Miura M.:
   "Apoptosis ensures spacing pattern formation of Drosophila sensory organs."
   Curr Biol. 21:278-87. 2011
5. Nakajima Y, Kuranaga E, Sugimura K, Miyawaki A, Miura M.:
   "Nonautonomous Apoptosis Is Triggered by Local Cell Cycle Progression during Epithelial Replacement in Drosophila."
   Mol Cell Biol. 31:2499-512. 2011
6. Koto, A., Kuranaga, E., and Miura, M.:
   "Temporal regulation of Drosophila IAP determines the dual functions of caspases in sensory organ development."
   J. Cell Biol. 187, 219-321, 2009
7. Tonoki A, Kuranaga E, Tomioka T, Hamazaki J, Murata S, Tanaka K, Miura M.:
   "Genetic evidence linking age-dependent attenuation of the 26S proteasome with the aging process."
   Mol Cell Biol. 29, 1095-106. 2009
8. Xue L, Igaki T, Kuranaga E, Kanda H, Miura M, Xu T.:
   "Tumor suppressor CYLD regulates JNK-induced cell death in Drosophila."
   Dev Cell. 13, 446-54. 2007
9. Kuranaga, E., Kanuka, H., Tonoki, A., Takemoto, K., Tomioka, T., Kobayashi, M., Hayashi, S., and Miura, M.:
   "Drosophila IKK-Related Kinase regulates non-apoptotic function of Caspases via degradation of IAPs."
   Cell 126, 583-596, 2006
10. Kuranaga E, Kanuka H, Igaki T, Sawamoto K, Ichijo H, Okano H, Miura M.:
    "Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila."
    Nature Cell Biol. 4, 705-710, 2002