Core Program members: Kazunori Nakajima
Department of Anatomy, Keio University School of Medicine
1982-1988: (M.D.) Keio University School of Medicine, Tokyo, Japan
1988-1990: Resident physician, Department of Internal Medicine, Keio University Hospital, Tokyo, Japan
1990-1994: (Ph.D.) Graduate School of Medicine, Osaka University, Osaka, Japan
1994-1995: Postdoctoral Research Fellow of the Japan Society for the Promotion of Science, the University of Tokyo, Tokyo, Japan
1995-1998: Research Scientist, Molecular Neurobiology Laboratory, Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan
1996-1998: Visiting Scientist, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, U.S.A.
1997-1998: Staff Scientist, Developmental Neurobiology Team, Developmental Brain Science Group, RIKEN Brain Science Institute, Saitama, Japan
1998-2001: Department Head & Assistant Professor, Department of Molecular Neurobiology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan
1999-2002: PRESTO Investigator, JST, Saitama, Japan
2001-2002: Department Head & Associate Professor, Department of Molecular Neurobiology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan
2002-present: Professor, Department of Anatomy, Keio University School of Medicine, Tokyo, Japan (2003-present: Department Chair)
2002-present: Guest Professor, Jikei University School of Medicine, Tokyo, Japan
Certificates and Degrees
1994: Ph.D. (Osaka University)
Major Research Area
Japanese Neurochemical Society
Japan Neuroscience Society
Japanese Society of Developmental Biologists
The Japanese Association of Anatomists
The Molecular Biology Society of Japan
Society for Neuroscience (U.S.A.)
"The Keio Journal of Medicine" Editorial Advisory Board (2002～)
"Developmental Brain Research" Editorial Board(2002～2005)
"Molecular and Cellular Biochemistry" Editorial Board(2004～)
"Brain Research" Editorial Board(2006～)
Division of Rolls in G-COE Program
Cell and molecular mechanisms of layer formation and its failure in the cerebral cortex
Mammals, including the human, develop cerebral cortex as the center of the various higher brain functions. In the cerebral cortex, excitatory neurons and inhibitory neurons are distributed in a well-balanced manner in multiple layers, with neurons sharing common features such as cellular morphology and targeting profiles get together to form a single layer. The construction of this multi-layered structure during development is fundamental to normal brain functions. Our group will investigate the mechanisms of the neuronal migration and layer formation in the developing cerebral cortex, focusing especially on the interplays between the intracellular and extracellular machineries that underlie these processes.
In the developing cerebral cortex, the majority of excitatory neurons is born near the ventricle and migrates radially toward the brain surface. Since late-born neurons migrate past their predecessors to reach beneath the marginal zone, the cortical plate is formed in an "inside-out" manner, with later-born neurons lying superficial to earlier-born neurons. Ultimately, the cortex develops into a 6-layered structure. In contrast to excitatory neurons, the majority of inhibitory cortical interneurons is generated in the ventral telencephalon (ganglionic eminences) and migrates tangentially into the pallium. Interestingly, these interneurons also migrate in an "inside-out" manner and are organized in birth date-specific layers.
Our group is investigating the mechanisms of the development of the functional cellular community in the cerebral cortex, focusing especially on the following 3 aspects.
1) What determines the destinations of neurons prior to their migration?
2) How is neuronal migration from their site of origin to their final locations regulated?
3) How do neurons form birth date-dependent layers after they reach beneath the marginal zone?
Identification of molecules preferentially expressed beneath the marginal zone in the developing cerebral cortex. Kashiko Tachikawa, Shinji Sasaki, Takuya Maeda, and Kazunori Nakajima. Neurosci. Res., in press.
Migratory behavior of presumptive interneurons is affected by AMPA receptor activation in slice cultures of embryonic mouse neocortex. Masato Yozu, Hidenori Tabata, Norbert Koenig, and Kazunori Nakajima. Dev. Neurosci., 30 (1-3), 105-116 (2008).
Computational cell model based on autonomous cell movement regulated by cell-cell signalling successfully recapitulates the "inside and outside" pattern of cell sorting. Takuya T Maeda, Itsuki Ajioka, and Kazunori Nakajima. BMC Systems Biology, 1, 43 (16 pages) (2007).
Regulation of the interaction of Disabled-1 with CIN85 by phosphorylation with Cyclin-dependent kinase 5. Yutaka Sato, Masato Taoka, Nami Sugiyama, Kenichiro Kubo, Takahiro Fuchigami, Akiko Asada, Taro Saito, Kazunori Nakajima, Toshiaki Isobe, and Shin-ichi Hisanaga. Genes to Cells,12 (12), 1315-1327 (2007).
Control of tangential/non-radial migration of neurons in the developing cerebral cortex. Kazunori Nakajima Neurochem. Int., 51 (2-4), 121-131 (2007).
The extremely conserved C-terminal region of Reelin is not necessary for secretion but is required for efficient activation of downstream signaling. Yoshimi Nakano, Takao Kohno, Terumasa Hibi, Shiori Kohno, Atsushi Baba, Katsuhiko Mikoshiba, Kazunori Nakajima, and Mitsuharu Hattori. J. Biol. Chem., 282 (28), 20544-20552 (2007).
Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex. Toshio Ohshima, Motoyuki Hirasawa, Hidenori Tabata, Tetsuji Mutoh, Tomoko Adachi, Hiromi Suzuki, Keiko Saruta, Takuji Iwasato, Shigeyoshi Itohara, Mitsuhiro Hashimoto, Kazunori Nakajima, Masaharu Ogawa, Ashok B. Kulkarni and Katsuhiko Mikoshiba. Development, 134 (12), 2273-2282 (2007).
Neurogenesis. Koji Oishi and Kazunori Nakajima. Encyclopedic Reference of Neuroscience, Springer-Verlag, in press.
Expression profiles of Insulin-like growth factor binding protein-like 1 in the developing mouse forebrain. Yuko Gonda, Hitoshi Sakurai, Yukio Hirata, Hidenori Tabata, Itsuki Ajioka, and Kazunori Nakajima. Gene Expr. Patterns,7 (4), 431-440 (2007).
Mouse Disabled1 (Dab1) is a nucleocytoplasmic shuttling protein. Takao Honda and Kazunori Nakajima. J. Biol. Chem., 281 (50), 38951-38965 (2006).
Large-scale correlation of DNA accession numbers to the cDNAs in the FANTOM full-length mouse cDNA clone set. Itsuki Ajioka*, Takuya Maeda*, and Kazunori Nakajima Keio J. Med., 55 (3), 107-110 (2006). (*equal contributors)
Identification of ventricular-side-enriched molecules regulated in a stage-dependent manner during cerebral cortical development. Itsuki Ajioka, Takuya Maeda, and Kazunori Nakajima Eur. J. Neurosci., 23(2), 296-308 (2006).
Disrupted-In-Schizophrenia-1 in development of the cerebral cortex: perturbation by its schizophrenia-associated mutation. Atsushi Kamiya, Ken-ichiro Kubo, Toshifumi Tomoda, Manabu Takaki, Richard Youn, Yuji Ozeki, Naoya Sawamura, Una Park, Chikako Kudo, Masako Okawa, Christopher A. Ross, Mary E. Hatten, Kazunori Nakajima, and Akira Sawa. Nature Cell Biol., 7 (12), 1067-1078 (2005).
Switching of α-catenin from αE-catenin in the cortical ventricular zone to αN-catenin II in the intermediate zone. Itsuki Ajioka and Kazunori Nakajima. Dev. Brain Res., 160(1),106-111 (2005).
The caudal migratory stream: A novel migratory stream of interneurons derived from the caudal ganglionic eminence in the developing mouse forebrain. Masato Yozu, Hidenori Tabata, and Kazunori Nakajima. J. Neurosci., 25 (31), 7268-7277 (2005).
Birthdate-dependent-segregation of the mouse cerebral cortical neurons in reaggregation cultures. Itsuki Ajioka and Kazunori Nakajima. Eur. J. Neurosci., 22 (2), 331-342 (2005).
Expression profiles of EphA3 at both the RNA and protein level in the developing mammalian forebrain. Chikako Kudo, Itsuki Ajioka, Yukio Hirata, and Kazunori Nakajima. J. Comp. Neurol., 487 (3), 255-269 (2005).
Neuronal migration in cortical development. Shigeaki Kanatani, Hidenori Tabata, and Kazunori Nakajima. J. Child Neurol., 20 (4), 274-279 (2005).
Birth-date dependent alignment of GABAergic neurons occurs in a different pattern from that of non-GABAergic neurons in the developing mouse visual cortex. Masato Yozu, Hidenori Tabata, and Kazunori Nakajima. Neurosci. Res., 49 (4), 395-403 (2004).
The Wnt/β-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Yusuke Hirabayashi, Yasuhiro Itoh, Hidenori Tabata, Kazunori Nakajima, Tetsu Akiyama, Norihisa Masuyama and Yukiko Gotoh. Development, 131 (12), 2791-2801 (2004).
Components of the Reelin signaling pathway are expressed in the spinal cord. Yee Ping Yip, Christine Capriotti, Susan Magdaleno, David Benhayon, Tom Curran, Kazunori Nakajima, and Joseph W. Yip. J. Comp. Neurol., 470 (2), 210-219 (2004).
Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex. Hidenori Tabata and Kazunori Nakajima. J. Neurosci., 23 (31), 9996-10001 (2003).
Segregation and coactivation of developing neocortical layer 1 neurons. Takeshi Soda, Ryo Nakashima, Dai Watanabe, Kazunori Nakajima, Ira Pastan, and Shigetada Nakanishi. J. Neurosci., 23 (15), 6272-6279 (2003).
Cellular and molecular mechanisms of neuronal migration in neocortical development. Takao Honda, Hidenori Tabata, and Kazunori Nakajima. Sem. in Cell & Develop. Biol., 14 (3), 169-174 (2003).
Cell and molecular mechanisms that control cortical layer formation in the brain. Ken-ichiro Kubo and Kazunori Nakajima. Keio J. Med., 52 (1), 8-20 (2003).
Neurons tend to stop migration and differentiate along the cortical internal plexiform zones in the Reelin signal-deficient mice. Hidenori Tabata and Kazunori Nakajima. J. Neurosci. Res., 69, 723-730, (2002).
Secreted Reelin molecules form homodimers. Ken-ichiro Kubo, Katsuhiko Mikoshiba, and Kazunori Nakajima. Neurosci. Res., 43, 381-388 (2002).
Efficient in utero gene transfer system to the developing mouse brains using electroporation-- Visualization of neuronal migration in the developing cortex. Hidenori Tabata and Kazunori Nakajima. Neuroscience, 103, 865-872 (2001).
Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody. Naoko Utsunomiya-Tate, Ken-ichiro Kubo, Shin-ichi Tate, Masatsune Kainosho, Eisaku Katayama, Kazunori Nakajima*, and Katsuhiko Mikoshiba. Proc. Natl. Acad. Sci. U.S.A., 97, 9729-9734 (2000). (*corresponding author)
Reelin controls position of autonomic neurons in the spinal cord. Joseph W. Yip, Yee Ping L. Yip, Kazunori Nakajima, Christine Capriotti. Proc. Natl. Acad. Sci. U.S.A., 97, 8612-8616 (2000).
The disabled 1 gene is disrupted by a replacement with L1 fragment in yotari mice. Toshio Kojima, Kazunori Nakajima*, and Katsuhiko Mikoshiba. Mol. Brain Res., 75, 121-127 (2000). (*corresponding author)
Thyroid hormone regulates reelin and dab1 expression during brain development. Manuel Alvarez-Dolado, Monica Ruiz, Jose A. del Rio, Soledad Alcantara, Ferran Burgaya, Michael Sheldon, Kazunori Nakajima, Juan Bernal, Brian W. Howell, Tom Curran, Eduardo Soriano, and Alberto Munoz. J. Neurosci., 19, 6979-6993 (1999).
Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice. S. Hossein Fatemi, Effat-Sadat Emamian, David Kist, Robert W. Sidwell, Kazunori Nakajima, Pervez Akhter, Anna Shier, Soheil Sheikh, and K. Bailey. Molecular Psychiatry, 4, 145-154 (1999).
Reelin regulates the development and synaptogenesis of the layer-specific entorhino-hippocampal connections. Victor Borrell, Jose A. Del Rio, Soledad Alcantara, Michele Derer, Albert Martinez, Gabriella D'Arcangelo, Kazunori Nakajima, Katsuhiko Mikoshiba, Paul Derer, Tom Curran, and Eduardo Soriano. J. Neurosci., 19, 1345-1358 (1999).
Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain. Dennis S. Rice, Michael Sheldon, Gabriella D'Arcangelo, Kazunori Nakajima, Dan Goldowitz, and Tom Curran. Development, 125, 3719-3729 (1998).
A truncated Reelin protein is produced but not secreted in the "Orleans" reeler mutation (Relnrl-Orl). Vinciane de Bergeyck, Kazunori Nakajima*, C. Lambert de Rouvroit, B. Naerhuyzen, Andre M. Goffinet, Takaki Miyata, Masaharu Ogawa, and Katsuhiko Mikoshiba. Mol. Brain Res., 50, 85-90 (1997). (*co-first author and corresponding author)
A novel neurological mutation of mouse, yotari, which exhibits reeler-like phenotype but expresses CR-50 antigen/Reelin. Hiroyuki Yoneshima, Eiichiro Nagata, Mineo Matsumoto, Maki Yamada, Kazunori Nakajima, Takaki Miyata, Masaharu Ogawa, and Katsuhiko Mikoshiba. Neurosci. Res. 29, 217-223 (1997).
scrambler and yotaridisrupt the disabled gene and produce a reeler -like phenotype in mice. Michael Sheldon, Dennis Rice, Gabriella D'Arcangelo, Hiroyuki Yoneshima, Kazunori Nakajima, Katsuhiko Mikoshiba, Brian W. Howell, Jonathan A. Cooper, Dan Goldowitz, and Tom Curran. Nature 389, 730-733 (1997).
Disruption of hippocampal development in vivo by CR-50, a monoclonal antibody against Reelin. Kazunori Nakajima*, Katsuhiko Mikoshiba, Takaki Miyata, Chikako Kudo, and Masaharu Ogawa. Proc. Natl. Acad. Sci. U.S.A. 94, 8196-8201 (1997). (*corresponding author)
Regulation of Purkinje cell alignment by Reelin as revealed with CR-50 antibody. Takaki Miyata, Kazunori Nakajima, Katsuhiko Mikoshiba, and Masaharu Ogawa. J. Neurosci. 17, 3599-3609 (1997).
A role for Cajal-Retzius cells and reelin in the development of hippocampal connections. Jose A. Del Rio, Bernd Heimrich, Victor Borrell, Eckart Foerster, Alexander Drakew, Soledad Alcantara, Kazunori Nakajima, Takaki Miyata, Masaharu Ogawa, Katsuhiko Mikoshiba, Paul Derer, Michael Frotscher, and Eduardo Soriano. Nature 385, 70-74 (1997).
Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody. Gabriella D'Arcangelo, Kazunori Nakajima, Takaki Miyata, Masaharu Ogawa, Katsuhiko Mikoshiba, and Tom Curran. J. Neurosci. 17, 23-31 (1997).
Astrocyte lineage analysis by detection of GFAP promoter activity in vitro. Noriyuki Morita, Kensuke Nakahira, Hiroko Baba, Hiromi Akita, Tatsuro Kumada, Masaharu Ogawa, Kazunori Nakajima, Mitsuhiro Kawata, Katsuhiko Mikoshiba, and Kazuhiro Ikenaka. Dev. Neurosci. 19, 210-218 (1997).