Neural Development, Brain Formation

2004/1- present:

Professor, Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Japan

1999/11-2003/12:

Research Scientist, Laboratory for Cell Culture Development (Dr. Masaharu Ogawa’s lab), Brain Science Institute, RIKEN, Japan

1998/10-1999/10:

Research Associate, Department of Neuroanatomy (Dr. Hideyuki Okano’s lab, Osaka University Graduate School of Medicine, Japan

1997/4-1998/9:

Postdoctoral Fellow, Department of Molecular, Cellular, and Developmental Biology (Dr. Jacqueline Lee's Lab), University of Colorado at Boulder, Colorado, USA

1996/4-1997/3:

Postdoctoral Fellow, Department of Molecular Neurobiology (Dr. Katsuhiko Mikoshiba's Lab), Institute for Medical Science, University of Tokyo, Japan

1994/4-1996/3:

Postdoctoral Fellow, Molecular Neurobiology Laboratory (Dr. Katsuhiko Mikoshiba's Lab), Tsukuba Life Science Center, RIKEN, Japan

1990/4-1994/3:

Graduate Student, Department of Physiology, Kochi Medical School, Japan (supervised by Dr. Masaharu Ogawa)

1988/5-1990/3:

Department of Otolaryngology and Head and Neck Surgery (Prof. Haruo Saito), Kochi Medical School Hospital

Studying molecular and cellular mechanisms of the brain formation

In 1990th, Takaki Miyata worked for the following two major projects: (1) Reelin. Ogawa and Mikoshiba team that he belonged obtained an antibody that specifically recognized normal but not reeler brains (Neuron 14, 899, 1995). What their antibody recognized was the product of reelin cloned by Curran’s group in the same year (Nature 374, 719, 1995). Miyata screened anti-Reelin hybridomas and also carried out blocking experiments by applying anti-Reelin to 3D cultures (J. Neurosci. 17, 3599, 1997). (2) NeuroD. Miyata worked in a lab led by Jacqueline Lee who found this bHLH factor (Science 268, 836, 1995), and analyzed the phenotype of neuroD-KO mice. He found that NeuroD is essential for differentiation of granule neurons in the developing cerebellar cortex and those in the hippocampal dendate gyrus (Genes & Dev. 13, 1647, 1999).

Then, Miyata has been working on neural progenitor cells. After contributing to prospectively identify neural stem cells in Hideyuki Okano’s lab, he moved to RIKEN BSI and developed a slice culture technique to observe 3D behaviors of neural progenitor cells. His report (Neuron 14, 899, 2001), together with Kriegstein lab’s work (Nature 409, 714, 2001), evidenced that “radial glial cells” are proliferative and neurogenic, not a quiescent guidepost as believed earlier. Miyata also demonstrated that radial glial fibers can be inherited by neurons and used for neuronal migration. His slice culture system was also useful to observe non-stem-like, intermediate progenitor cells (Development 131, 3133, 2004) and to carry out microsurgical and pharmacological experiments to dissect mechanical aspects of neocortical development (Curr. Biol. 17, 146, 2007).

In this Global COE program, Miyata will further dissect the cellular and molecular mechanisms of brain formation. Akira Sakakibara (Assist. Prof. who joined Miyata lab in April 2008: ref. 8) will lead intracellular molecular imaging in 3D tissues. Ayano Kawaguchi (Assoc. Prof. who joined in September 2008) will extend her single-cell gene profiling analysis (Ref. 1) and couple it with morphological analysis. Fundamental knowledge of mouse brain development should then be utilized for the elucidation of causes of congenital human brain anomalies and occurrence/progression of human brain tumors, as well as development of therapeutic approaches to potentially rescue structural abnormalities in the developing and adult brains.

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1. Kawaguchi A et al. Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis. Development 135: 3113-3124 (2008)
2. Yoon KJ et al. Mind bomb 1-experssing intermediate progenitors generate Notch signaling to maintain radial glial cells. Neuron 58: 519-531 (2008)
3. Sunabori T et al. Cell-cycle-specific nestin expression coordinates with morphological changes in embryonic cortical neural progenitors. J. Cell Sci. 121: 1204-1212 (2008)
4. Sakaue-Sawano A et al. Spatio-temporal dynamics of multicellular cell cycle progression. Cell 132: 487-498 (2008)
5. Konno D et al. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat. Cell Biol. 10: 93-101 (2008)
6. Miyata T et al. Twisting of neocortical progenitor cells underlies a spring-like mechanism for daughter cell migration. Curr. Biol. 17: 146-151 (2007)
7. Tamai H et al. Pax6 transcription factor is required for the interkinetic nuclear movement of neuroepithelial cells. Genes Cells 12: 983-996 (2007)
8. Sakakibara A et al. Mechanism of polarized protrusion formation on neuronal precursors migrating in the developing chicken cerebellum. J. Cell Sci. 119: 3583-3592 (2006)
9. Hirai S et al. The c-Jun N-terminal kinase activator dual leucine zipper kinase regulates axon growth and neuronal migration in the developing cerebral cortex. J. Neurosci. 26: 11992-12002 (2006)
10. Imai F et al. Inactivation of aPKCl results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex. Development 133: 1735-1744 (2006)
11. Naruse M et al. Induction of oligodendrocyte progenitors in dorsal forebrain by intraventricular microinjection of FGF-2. Dev. Biol. 60: 1084-1100 (2006)
12. Kawaguchi A et al. Differential expression of Pax6 and Ngn2 between pair-generated cortical neurons. J. Neurosci. Res. 78: 784-795 (2004)
13. Miyata T et al. Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131: 3133-3145 (2004)
14. Shinozaki K et al. Absence of Cajal-Retzius cells and subplate neurons associated with defects of tangential migration from ganglionic eminence in Emx1/2 double mutant cerebral cortex. Development 129: 3479-3492 (2002)
15. Miyata T et al. Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31: 727-741 (2001)
16. Kawaguchi A et al. Nestin-EGFP mice: visualization of the self-renewal and multipotency of CNS stem cells. Mol. Cell. Neurosci.17: 259-273 (2001)
17. Nakamura Y et al. The bHLH gene Hes1 as a repressor of neuronal commitment of the CNS stem cells. J. Neurosci. 20: 283-293 (2000)
18. Miyata T et al. NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. Genes & Dev. 13: 1647-1652 (1999)
19. Miyata T et al. Regulation of Purkinje cell alignment by Reelin as revealed with CR-50 antibody. J. Neurosci. 17: 3599-3609 (1997)
20. Del Rio J et al. A role for Cajal-Retzius cells and reelin in the development of hippocampal connections. Nature 385: 70-74 (1997)
21. Ogawa M et al. The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons. Neuron 14: 899-912 (1995)