Welcome to Laboratory of Molecular Biology's Homepage!

Research Interests

The human body is composed of hundreds of different cell types that each perform distinct functions but which (except for the germline) all contain the same genetic information. A fundamental question with regard to tissue development is how tissue stem cells or multipotent progenitor cells give rise to various cell types in appropriate numbers and at the right locations to achieve tissue organization. Our laboratory has focused on identifying the mechanisms and logic that underlie the regulation of neural stem-progenitor cell fate both during embryonic brain development and in adulthood.

We are currently investigating genetic and epigenetic regulation of neural stem-progenitor cell fate and neuronal maturation as well as the genesis and maintenance of adult neural stem cells. We are also studying the relevance of these processes to neurodevelopmental disorders.

Ongoing research projects

  1. Investigation of the mechanisms responsible for the regulation of neural stem-progenitor cell fate during neocortical development
    • Roles of chromatin modifiers such as Polycomb group proteins in regulation of neural stem-progenitor cell fate during the expansion, neurogenic, and gliogenic phases
    • Signaling pathways that regulate the fate commitment and differentiation of neural stem/progenitor cells
    • Mechanisms that determine the identity and size of cortical areas
  2. Investigation of genetic and epigenetic regulation of neuronal differentiation-maturation and activation
    • Roles of chromatin modifiers in neuronal differentiation-maturation (including axonal and dendritic development and synapse formation) and activation processes
    • Their roles in the critical period
    • Roles of major satellites in cell fate regulation
  3. Investigation of the embryonic origin of adult neural stem cells
    • The identity and diversity of embryonic precursors (“origin”) of adult neural stem cells - characterization of these precursors in comparison with other embryonic neural progenitor cells that contribute to brain development
    • The niche signals for establishment and maintenance of these precursor cells
    • Epigenetic modifiers that regulate the differentiation potential of these precursor cells
  4. Investigation of dysregulation of neural stem-progenitor cell fate in neurodevelopmental disorders
    • Relevance to psychiatric conditions such as autism spectrum disorder
  5. Investigation of innate immune responses and their relation to brain development
    • Basic mechanisms of cellular responses to viral infection
    • Interorganelle interactions and their roles in stress responses
    • Effects of maternal immune activation on brain development, in particular on neural stem-progenitor cell fate, and their relevance to neurodevelopmental disorders such as autism spectrum disorder and schizophrenia

Selected Recent Publications (2008 to Present)

Harada Y, Yamada K, Imayoshi I, Kageyama R, Suzuki Y, Kuniya T, Furutachi S, Kawaguchi D, Gotoh Y.
Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module.
Nat. Commun., 12(1):6562, 2021.
Yuizumi, N., Harada Y., Kuniya T., Sunabori T., Koike M., Wakabayashi M., Ishihama Y., Suzuki Y., Kawaguchi D., Gotoh Y.
Maintenance of neural stem - progenitor cells by the lysosomal biosynthesis regulators TFEB and TFE3 in the embryonic mouse telencephalon.
Stem Cells, 39:929-944, 2021.
Omiya, H., Yamaguchi, S., Watanabe, T., Kuniya, T., Harada, Y., Kawaguchi, D., Gotoh, Y.
BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors.
Sci. Rep., 11, 613, 2021.
Eto H, Kishi Y, Yakushiji-Kaminatsu N, Sugishita H, Utsunomiya S, Koseki H, Gotoh Y.
The Polycomb group protein Ring1 regulates dorsoventral patterning of the mouse telencephalon.
Nat. Comm., 11, 5709, 2020.
Aoyama-Ishiwatari, S., Okazaki, T., Iemura, S., Natsume, T., Okada, Y., Gotoh, Y.
NUDT21 links mitochondrial IPS-1 to RLR-containing stress granules and activates host antiviral defense.
J. Immunol., 206, 2020.
Imaizumi Y, Furutachi S, Watanabe T, Miya H, Kawaguchi D, Gotoh Y.
Role of the imprinted allele of the Cdkn1c gene in mouse neocortical development.
Sci Rep., 10(1):1884, 2020.
Tsuboi M, Hirabayashi Y, Gotoh Y.
Diverse gene regulatory mechanisms mediated by Polycomb group proteins during neural development.
Curr. Opin. Neurobiol., 59:164-173, 2019. Review.
Tanaka H, Okazaki T, Aoyama S, Yokota M, Koike M, Okada Y, Fujiki Y, Gotoh Y.
Peroxisomes control mitochondrial dynamics and the mitochondrion-dependent pathway of apoptosis.
J. Cell Sci., 132(11), 2019.
Tsuboi M, Kishi Y, Yokozeki W, Koseki H, Hirabayashi Y, Gotoh Y.
Ubiquitination-Independent Repression of PRC1 Targets during Neuronal Fate Restriction in the Developing Mouse Neocortex.
Dev Cell., 47(6):758-772.e5, 2018.
Kishi, Y. and Gotoh, Y.
Regulation of chromatin structure during neural development.
Frontiers Neurosci., 12:874, 2018. Review.
Lanjakornsiripan, D., Pior, B. J., Kawaguchi, D., Furutachi, S., Tahara, T., Katsuyama, Y., Suzuki, Y., Fukazawa, F., and Gotoh, Y.
Layer-specific heterogeneity of astrocytes and its dependence on neuronal layers.
Nat. Commun., 9, 1623, 2018.
Kawai, H., Kawaguchi, D., Kuebrich, B. D., Kitamoto, T., Yamaguchi, M., Gotoh, Y., and Furutachi, S.
Area-specific regulation of quiescent neural stem cells by Notch3 in the adult mouse subependymal zone.
J. Neurosci., 37, 11867-11880, 2017.
Nagao M, Ogata T, Sawada Y, Gotoh Y.
Zbtb20 promotes astrocytogenesis during neocortical development.
Nat. Commun., 7, 11102, 2016.
Itoh Y, Higuchi M, Oishi K, Kishi Y, Okazaki T, Sakai H, Miyata T, Nakajima K, Gotoh Y.
PDK1-Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex.
Proc. Natl. Acad. Sci. U.S.A., 113(21):E2955-64, 2016.
Furutachi S, Miya H, Watanabe T, Kawai H, Yamasaki N, Harada Y, Imayoshi I, Nelson M, Nakayama KI, Hirabayashi Y, Gotoh Y.
Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells.
Nat. Neurosci. 18, 657-65, 2015.
Highlighted by a News and Views article of Nat. Neurosci.
Okazaki T, Higuchi M, Takeda K, Iwatsuki-Horimoto K, Kiso M, Miyagishi M, Yanai H, Kato A, Yoneyama M, Fujita T, Taniguchi T, Kawaoka Y, Ichijo H, Gotoh Y.
The ASK family kinases differentially mediate induction of type I interferon and apoptosis during the antiviral response.
Sci. Signal., 8, ra78, 2015.
Morimoto-Suzki N, Hirabayashi Y, Tyssowski K, Shinga J, Vidal M, Koseki H, Gotoh Y.
The polycomb component Ring1B regulates the timed termination of subcerebral projection neuron production during mouse neocortical development.
Development 141, 4343-53, 2014.
Selected by "Faculty of 1000"
Kawaguchi, D., Furutachi, S., Kawai, H., Hozumi, K. and Gotoh, Y.
Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.
Nat. Commun. 4, 1880, 2013.
Furutachi, S., Matsumoto, A., Nakayama, K.I. and Gotoh, Y.
p57 controls adult neural stem cell quiescence and modulates the pace of lifelong neurogenesis.
EMBO J. 32, 970-981, 2013.
Itoh, Y., Moriyama, Y., Hasegawa, T., Endo, T.A., Toyoda, T. and Gotoh, Y.
Scratch regulates neuronal migration onset via an epithelial-mesenchymal transition-like mechanims.
Nat. Neurosci. 16, 416-425, 2013.
Itoh, Y.*, Tyssowski, K.* and Gotoh, Y.
(*These authors contributed equally to this review.)
Transcriptional coupling of neuronal fate commitment and the onset of migration.
Curr. Opin. Neurobiol., 23, 957-64, 2013. Review.
Kishi, Y., Fujii, Y., Hirabayashi, Y. and Gotoh, Y.
HMGA proteins regulate global chromatin state and the neurogenic potential in neocortical precursor cells.
Nat. Neurosci. 15, 1127-1133, 2012.
Onoguchi, M., Hirabayashi, Y., Koseki, H. and Gotoh, Y.
A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development.
Proc. Natl. Acad. Sci. U.S.A. 109, 16939-16944, 2012.
Hirabayashi, Y. and Gotoh, Y.
Epigenetic control of neural precursor cell fate during development.
Nat. Rev. Neurosci., 11, 377-88, 2010. Review.
Kuwahara, A., Hirabayashi, Y., Knoepfler, P.S., Taketo, M.M., Sakai, J., Kodama, T. and Gotoh, Y.
Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex.
Development 137, 1035-1044, 2010.
Hirabayashi, Y., Suzki, N., Tsuboi, M., Endo, T.A., Toyoda, T., Shinga, J., Koseki, H., Vidal, M. and Gotoh, Y.
Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition.
Neuron 63, 600-613, 2009.
Oishi, K., Watatani, K., Itoh, Y., Okano, H., Guillemot, F., Nakajima, K. and Gotoh, Y.
Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1.
Proc. Natl. Acad. Sci. U.S.A. 106, 13064-13069, 2009.
Higuchi, M., Onishi, K., Yoneyama, C. and Gotoh, Y.
Scaffolding function of PAK in the PDK1-Akt pathway.
Nat. Cell Biol. 10, 1356-1364, 2008.
Kawaguchi, D., Yoshimatsu, T., Hozumi, K. and Gotoh, Y.
Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon.
Development 135, 3849-3858, 2008.
Mori, Y., Higuchi, M., Hirabayashi, Y., Fukuda, M. and Gotoh, Y.
JNK phosphorylates Syt 4 and enhances Ca2+-evoked release.
EMBO J. 27, 76-87, 2008.
More ⇒ Published Papers   

Graduate School of Pharmaceutical Sciences, The University of Tokyo
Institute of Molecular and Cellular Biosciences, The University of Tokyo
Department of Chemistry and Biotechnology, School of Engineering,
The University of Tokyo
Department of Integrated Biosciences, The Graduate School of Frontier Sciences,
The University of Tokyo
JST-CREST Basic Reaserch Programs "Elucidation of the Principles of Formation and Function of the Brain Neural Network and Creation of Control Technologies"
JST-CREST Basic Reaserch Programs "Innovation for Ideal Medical Treatment Based on the Understanding of Maintenance, Change and Breakdown Mechanisms of Homeostasis among Interacting Organ Systems"
IRCN International Research Center for Neurointelligence