Graduate School of Medicine / School of Medicine, Faculty of Medicine

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Developmental & Integrative Neuroscience

Molecular and Cellular Neurobiology

We are studying the cells in the CNS from their birth to death. We aim at the elucidation of molecular basis for the control of proliferation, differentiation, and survival of neural precursor cells, hoping that our results will contribute to the treatment of intractable CNS diseases in the near future. We are also studying the interaction between neural cells and vascular cells (especially of cerebral microvessels). Furthermore, we aim at elucidation of molecular basis for the control of neuronal excitation. We welcome anyone who is interested in our work. Please don’t hesitate to contact us.

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Professor Minamishima Andrew Yoji ,M.D., Ph.D.
Assistant Professor Masashi Kurachi, Ph.D.
Masae Masae, Ph.D.
Hanako Yamamoto, Ph.D.

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Research & Education

Research content

Control of survival, proliferation, and differentiation of neural precursor cells
Even in the presence of saturating amounts of mitogens, cerebellar granule cell precursors (GCPs) exit the cell cycle and differentiate into postmitotic neurons. We have found that p27/Kip1, a cyclin-dependent kinase inhibitor, plays a crucial role in the control of GCP proliferation and differentiation (J. Neurosci. 2000). We are also interested in the plasticity of GCPs. GCPs have long been regarded as being committed to granule cells, but we have got several lines of evidence that these cell can also differentiate into astroglial cells (PNAS 2004). ?We also showed that CD44-positive cells are candidates for astrocyte precursor cells in developing cerebellum (Cerebellum 2012).

Interaction between neural cells and vascular cells
We showed that brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage (Brain Res. 2012). We are now studying the molecular basis for this interaction between neural cells and vascular cells.

Control of neuronal excitation by TRP channels
We are studying control of neuronal excitation by TRP channels using TRPV4 knockout mice. We are also examining the subpopulation of astrocytes which play a role for control of neuronal excitation.

Business education

Undergraduate education
In conjunction with department of biochemistry, we teach biochemistry to undergraduate students.

Graduate education
In the first year, students do several short-term laboratory projects, to learn various techniques. They also attend a number of courses on specialized areas of neurobiology. The remaining three years are then spent doing a PhD in our laboratory.

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Clinical Activities

(no clinical assignments)

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Citizenship Activities

We believe that our research in developmental neurobiology will contribute to the treatment of intractable CNS diseases in the near future. We endeavor to inform high school students and laymen of the recent advances in developmental neurobiology at open seminars.

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1. Shibasaki K, Tominaga M, Ishizaki Y: Hippocampal neuronal maturation triggers post-synaptic clustering of brain temperature-sensor TRPV4. Biochem. Biophys. Res. Commun. 458: 168-173, 2015.

2. Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-Semba R, Sekine Y, Sato Y, Saruta C, Ishizaki Y, Yuzaki M, Kojima M, Furuichi T: Axonal localization of Ca2+-dependent activator protein for secretion 2 is critical for subcellular locality of brain-derived neurotrophic factor and neurotrophin-3 release affecting proper development of postnatal mouse cerebellum. PloS one 9: e99524, 2014.

3. Shibasaki K, Ikenaka K, Tamalu F, Tominaga M, Ishizaki Y: A novel subtype of astrocytes expressing TRPV4 regulates neuronal excitability via release of gliotransmitters. J. Biol. Chem. 289: 14470-14480, 2014.

4. Shibasaki K, Ishizaki Y, Mandadi S: Astrocytes functionally express TRPV2 channel. Biochem Biophys Res Commun 441: 327-332, 2013.

5. Sadakata T, Kakegawa W, Shinoda Y, Hosono M, Katoh-Semba R, Sekine Y, Sato Y, Tanaka M, Iwasato T, Itohara S, Furuyama K, Kawaguchi Y, Ishizaki Y, Yuzaki M, Furuichi T: CAPS1 deficiency perturbs dense-core vesicle trafficking and Golgi structure and reduces presynaptic release probability in the mouse brain. J Neurosci 33: 17326-17334, 2013.

6. Okano-Uchida T, Naruse M, Ikezawa T, Shibasaki K, Ishizaki Y: Cerebellar neural stem cells differentiate into two distinct types of astrocytes in response to CNTF and BMP2. Neurosci. Lett. 552: 15-20, 2013.

7. Naruse M, Shibasaki K, Yokoyama S, Kurachi M, Ishizaki Y: Dynamic Changes of CD44 Expression from Progenitors to Subpopulations of Astrocytes and Neurons in Developing Cerebellum. PloS one 8: e53109, 2013.

8. Matsumoto H, Shibasaki K, Uchigashima M, Koizumi A, Kurachi M, Moriwaki Y, Misawa H, Kawashima K, Watanabe M, Kishi S, Ishizaki Y: Localization of acetylcholine-related molecules in the retina: implication of the communication from photoreceptor to retinal pigment epithelium. PloS one 7: e42841, 2012.

9. Puentes S, Kurachi M, Shibasaki K, Naruse M, Yoshimoto Y, Mikuni M, Imai H, Ishizaki Y: Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage. Brain Res. 1469: 43-53, 2012.

10. Cai N, Kurachi M, Shibasaki K, Okano-Uchida T, Ishizaki Y: CD44-positive cells are candidates for astrocyte precursor cells in developing mouse cerebellum, Cerebellum 11: 181-193, 2012.

11. Feng L, Eisenstat DD, Chiba S, Ishizaki Y, Shibasaki K: Brn-3b inhibits generation of amacrine cells by binding to and negatively regulating DLX1/2 in developing retina. Neuroscience 195: 9-20, 2011.

12. Kiyohara H, Ishizaki Y, Suzuki Y, Katoh H, Hamada N, Ohno T, Takahashi T, Kobayashi Y, Nakano T: Radiation-induced ICAM-1 expression via TGF-1 pathway on human umbilical vein endothelial cells; comparison between X-ray and carbon-ion beam irradiation. J. Radiat. Res. 52: 287-292, 2011.

13. Ibhazehiebo K, Iwasaki T, Okano-Uchida T, Shimokawa N, Ishizaki Y, Koibuchi N: Suppression of thyroid hormone receptor-mediated transcription and disruption of thyroid hormone-induced cerebellar morphogenesis by the polybrominated biphenyl mixture, BP-6. NeuroToxicology 32: 400-409, 2011.

14. Saito T, Shibasaki K, Kurachi M, Puentes S, Mikuni M, Ishizaki Y: Cerebral capillary endothelial cells are covered by the VEGF-expressing foot processes of astrocytes.  Neurosci. Lett. 497: 116-121, 2011.

15. Shibasaki K, Murayama N, Ono K, Ishizaki Y, Tominaga M: TRPV2 enhances axon outgrowth through its activation by membrane stretch in developing sensory and motor neurons. J. Neurosci. 30: 4601-4612, 2010.

16. Akahoshi N, Kobayashi C, Ishizaki Y, Izumi T, Himi T, Suematsu M, Ishii I: Genetic background conversion ameliorates semi-lethality and permits behavioral analyses in cystathionine {beta}-synthase-deficient mice, an animal model for hyperhomocysteinemia. Hum. Mol. Genet. 17: 1944-200, 2008.

17. Ishizaki Y: Control of proliferation and differentiation of neural precursor cells: focusing on the developing cerebellum. J. Pharmacol. Sci. 101:183-188, 2006.

18. Akahoshi N, Izumi T, Ishizaki Y, Ishii I: Differential induction of cystathionine gamma-lyase in the livers and kidneys of mouse dams during gestation and lactation. Biol. Pharm. Bull. 29:1799-1802, 2006.

19. Okano-Uchida T, Himi T, Komiya Y, Ishizaki Y: Cerebellar granule cell precursors can differentiate into astroglial cells. Proc. Natl. Acad. Sci. USA 101:1211-1216, 2004.

20. Okano-Uchida T, Okumura E, Iwashita M, Yoshida H, Tachibana K, Kishimoto T: Distinct regulators for Plk1 activation in starfish meiotic and early embryonic cycles. EMBO J. 22: 5633-5642, 2003.

21. Miyazawa K, Himi T, Garcia V, Yamagishi H, Sato S, Ishizaki Y: A role for p27/Kip1 in the control of cerebellar granule cell precursor proliferation. J. Neurosci. 20:5756-5763, 2000.

22. Maeno E, Ishizaki Y, Kanaseki T, Hazama A, Okada Y: Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc. Natl. Acad. Sci. USA 97:9487-9492, 2000.

23. Ishizaki Y, Jacobson MD, Raff MC: A role for caspases in lens fiber differentiation. J. Cell Biol.140:153-158, 1998.

24. Ishizaki Y, Cheng L, Mudge AW, Raff MC: Programmed cell death by default in embryonic cells, fibroblasts, and cancer cells. Mol. Biol. Cell 6:1443-1458, 1995.

25. Ishizaki Y, Burne JF, Raff MC: Autocrine signals enable chondrocytes to survive in culture. J. Cell Biol. 126:1069-1077, 1994.

26. Ishizaki Y, Voyvodic JT, Burne JF, Raff MC: Control of lens epithelial cell survival. J. Cell Biol. 121: 899-908, 1993.

27. Raff MC, Barres BA, Burne JF, Coles HS, Ishizaki Y, Jacobson MD: Programmed cell death and the control of cell survival: lessons from the nervous system. Science 262:695-700,1993.

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1988 Department of Molecular and Cellular Neurobiology was newly established.
1988 Professor Yoshiaki Komiya arrived.
1989 Associate professor Tomoko Tashiro, and assistant professor Michihiro Igarashi arrived.
1990 Assistant professor Sumito Sekimoto arrived (~ 1995).
1992 Assistant professor Takeo Sugaya arrived (~ 1993).
1996 Assistant professor Katsumi Ohbayashi arrived (~1997).
1997 Assistant professor Masashi Kurachi arrived.
2000 Associate professor Tomoko Tashiro was promoted to professor at Aoyama Gakuin University.
2000 Assistant professor Michihiro Igarashi was promoted to associate professor.
2000 Associate professor Michihiro Igarashi was promoted to professor at Niigata University.
2000 Associate professor Yasuki Ishizaki arrived.
2001 Assistant professor Takayuki Okano-Uchida arrived.
2004 Professor Yoshiaki Komiya retired.
2004 Associate professor Yasuki Ishizaki was promoted to professor.
2005 Associate professor Isao Ishii arrived.
2009 Associate professor Isao Ishii moved to Keio University School of Medicine.
2009 Lecturer Koji Shibasaki arrived.
2010 Assistant professor Takayuki Okano-Uchida resigned.
2010 Assistant professor Masae Naruse arrived.
2011 Assistant professor Hanako Yamamoto arrived.
2012 Lecturer Koji Shibasaki was promoted to associate professor.