Kazuhito Toyooka, Ph.D.
Assistant Professor, Dept. Neurobiology and Anatomy,
Drexel University College of Medicine
Email: ktoyooka@drexelmed.edu

Mechanisms of Neuronal Migration in the Developing Cerebral Cortex and Hippocampus


 

 

Research and Interest

Adobe SystemsOur lab has been studying the mechanisms of neuronal migration in the developing cerebral cortex and hippocampus. To uncover these mechanisms, we have focused on the 14-3-3 proteins.

            Neurogenesis and neuronal migration require the precise choreography of more than 100 billion neuronal cells which form appropriate connections during brain development. However, the disruption of neurogenesis and neuronal migration results in a wide range of diseases including brain morphological disorders such as lissencephaly and Miller-Dieker syndrome (MDS) and mental illnesses such as autism and schizophrenia. Our goals are to understand the mechanisms of neuronal migration that are required to form appropriate neuronal connections and to clarify the roles of the multifunctional 14-3-3 protein family in brain development and behaviors in conjunction with human diseases. To achieve these goals, we have been using multiple approaches including mouse genetic techniques and time-lapse live imaging using brain slices.

Biography

Kazuhito Toyooka graduated from Shizuoka University in Japan and received his Ph.D. in Immunology at Osaka University in Japan. He did post-doctoral fellowships at the University of California San Diego and the University of California San Francisco. He also served on the faculty at Osaka City University School of Medicine in Japan. He was appointed to the faculty in the Department of Neurobiology and Anatomy at Drexel University College of Medicine in 2013.

Ongoing Projects Adobe Systems

1)      The analysis of the Functions of the 14-3-3 proteins in neuronal migration in the cerebral cortex and the  hippocampus

2)      The understanding of the etiology of Lissencephaly/Miller Dieker syndrome

3)      The analysis of the functions of the 14-3-3 proteins in behaviors in conjunction with human mental illnesses such as autism and schizophrenia    

Lab Personnel

Tomoka Wachi, PhD, Postdoctoral Fellow

Brett T.Cornell, PhD candidate (Neuroscience)

Previous Lab MembersAdobe Systems

Thomas Sibert

Courtney Marshall

 

Publications

Peer-reviewed manuscripts

Wachi T, Cornell B, Marshall C, Zhukarev V, Baas PW, Toyo-Oka K. Ablation of the 14-3-3gamma Protein Results in Neuronal Migration Delay and Morphological Defects in the Developing Cerebral Cortex. Dev Neurobiol. 2015 Aug 22. doi: 10.1002/dneu.22335. [Epub ahead of print]

 Toyo-oka K, Wachi T, Hunt RF, Baraban SC, Taya S, Ramshaw H, Kaibuchi K, Schwarz QP, Lopez AF, Wynshaw-Boris A.,14-3-3ε and ζ regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain. J Neurosci. 2014 Sep 3;34:12168-12181.

Kosaka, Y., Cieslik, K., A, Li, L., Lezin, G, Maguire, C., T., Saijoh, Y., Toyo-Oka, K., Gambello, M., J., Vatta, M., Wynshaw-Boris, A., Baldini, A., Yost, H., J. and Brunelli, L. 14-3-3{varepsilon} Plays a Role in Cardiac Ventricular Compaction by Regulating the Cardiomyocyte Cell Cycle. Mol. Cell. Miol., 2012, 32:5089-5102

Cheah, P.-S., Ramshaw, H. S., Thomas, P. Q., Toyo-oka, K., Martin, S., Coyle, P., Guthridge, M. A., Stomski, F., Maarten van den Buuse, Wynshaw-Boris, A., Lopez, A. F. and Schwarz, Q. P. Neurodevelopmental defects and neuropsychiatric behaviour arise from 14-3-3zeta deficiency. Mol. Psychiatr., 2011, 17:451-466..

Ikeda, M., Hikita, T., Taya, S., Uraguchi-Asaki, J., Toyo-oka, K., Wynshaw-Boris, A., Ujike, H., Inada, T., Takao, K., Miyakawa, T., Osaki, N., Kaibuchi, K. and Iwata, N. Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia. Hum. Mol. Genet., 2008, 17: 3212-3222

Yingling, J., Youn, Y. H., Darling, D., Toyo-oka, K., Pramparo, T., Hirotsune, S. and Wynshaw-Boris, A. Neuroepithelial Stem Cell Proliferation requires LIS1 for Precise Spindle Orientation and Symmetric Division. Cell, 2008, 132: 474-486.

Toyo-oka, K., Yano, Y., Shiota, M., Iwao, H., Hiraiwa, N., Muramatsu, M., Yoshiki, A. and Hirotsune, S. Protein Phosphatase4 catalytic subunit (PP4c) regulates CDK1 activity and organization of microtubules through dephosphorylation of NDEL1, J. Cell Biol., 2008, 180: 1133-1147.

Mori, D., Yano, Y., Toyo-oka, K., Yoshida, N., Yamada, M., Muramatsu, M., Zhang, D., Saya, H., Toyoshima, Y. Y., Kinoshita, K., Wynshaw-Boris, A. and Hirotsune, S. NDEL1 Phosphorylation by Aurora-A Kinase Is Essential for Centrosomal Maturation, Separation, and TACC3 recruitment. Mol. Cell. Biol., 2007, 27: 352-367.

Toyo-oka, K., Bowen,T. J., Hirotsune, S., Li, Z., Jain, S., Ota, S., Lozach, L. E., Bassett, I. G., Lozach, J., Rosenfeld, M. G., Glass, C. K., Eisenman, R., Ren, B., Hurlin, P. J. and Wynshaw-Boris, A. Mnt-Deficient Mammary Glands Exhibit Impaired Involution and Tumors with Characteristics of Myc Overexpression. Cancer Res., 2006, 66: 5565-5573.

Toyo-oka, K., Sasaki, S., Yano, Y., Mori, D., Kobayashi, T., Toyoshima, Y. Y., Tokuoka, S. M., Ishii, S., Shimizu, T., Muramatsu, M., Hiraiwa, N., Yoshiki, A., Wynshaw-Boris, A. and Hirotsune, S. Recruitment of katanin P60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration. Hum. Mol. Genet., 2005, 14: 3113-3128.

Sasaki, S., Mori, D., Toyo-oka, D., Chen, A., Garrett-Beal, L., Muramatsu, M., Miyagawa, S., Hiraiwa N., Yoshiki, A., Wynshaw-Boris, A., and Hirotsune, A. Complete Loss of Ndel1 Results in Neuronal Migration Defects and Early Embryonic Lethality. Mol. Cell. Biol., 2005, 25:7812-7827.

Toyo-oka, K., Hirotsune, S., Gambello, M. J., Zhou, Z.-Q., Olson, L., Rosenfeld, M. G., Eisenman, R., Hurlin, P. J. and Wynshaw-Boris, A. Loss of the Max-interacting protein Mnt in mice results in decreased viability, defective embryonic growth and craniofacial defects: relevance to Miller-Dieker syndrome. Hum. Mol. Genet., 2004, 13:1057-1067.

Hurlin, P. J., Zhou, Z.-Q., Toyo-oka, K., Ota, S., Walker, W. L., Hirotsune, S. and Wynshaw-Boris, A. Evidence of Mnt-Myc Antagonism Revealed by Mnt Gene Deletion. Cell Cycle, 2004, 3:97-99.

Hurlin, P. J., Zhou, Z.-Q., Toyo-oka, K., Ota, S., Walker, W. L., Hirotsune, S. and Wynshaw-Boris, A. Deletion of Mnt leads to disrupted cell cycle control and tumorigenesis. EMBO J., 2003, 22:4584-4596.

Toyo-oka, K., Shionoya, A., Gambello, M. J., Cardoso, C., Leventer, R., Ward, H. L., Ayala, R., Tsai, L.-H., Dobyns, W., Ledbetter, D., Hirotsune, S. and Wynshaw-Boris, A. 14-3-3epsilon is important for neuronal migration via binding of NUDEL : a molecular explanation for Miller-Dieker syndrome. Nat. Genet., 2003, 34:274-285.

Cardoso, C., Leventer, R. J., Ward, H. L., Toyo-oka, K., Chung, J., Gross, A., Martin, C. L., Allanson, J., Pilz, D. T., Olney, A. H., Mutchinick, O. M., Hirotsune, S., Wynshaw-Boris, A., Dobyns, W. B. and Ledbetter, D. H. Refinement of a 400-kb Critical Region Allows Genotypic Differentiation between Isolated Lissencephaly, Miller-Dieker Syndrome, and Other Phenotypes Secondary to Deletions of 17p13.3. Am. J. Hum. Genet., 2003, 72:918-930.

Merscher, S., Funke, B, Epstein, J. A., Heyer, J., Puech, A., Lu, M. M., Xavier, R. J., Demay, M. B., Russell, R. G., Factor, S., Toyooka, K., Jore, B. S., Lopez, M., Pandita, R. K., Lia, M., Carrion, D., Xu, H., Schorle, H., Kobler, J. B., Scambler, P., Wynshaw-Boris, A., Skoultchi, A. I., Morrow, B. E. and Kucherlapati1, R. Tbx1 is Responsible for Cardiovascular Defects in Velo-Cardio-Facial/DiGeorge Syndrome. Cell, 2001, 104:619-629.

The RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium. Functional annotation of full-length mouse cDNA collection. Nature. 2001, 409:685-690. (85th out of 95 authors)

Reviews

Wachi T. and Toyo-okaK., Novel Functions of 14-3-3 Proteins in Neurogenesis and Neuronal Differentiation In Vivo. Ther Targets Neurol Dis (Therapeutic targets for neurological diseases), 2015, 2(1), doi: 10.14800/ttnd.500

 

Yingling, J., Toyo-oka, K., and Wynshaw-Boris, A.. Miller- Dieker Syndrome: Analysis of a Human Contiguous Gene Syndrome in the Mouse. Am. J. Hum. Genet., 2003, 73(3):475-488.