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Laboratory for Developmental Gene Regulation
Hitoshi OKAMOTO
Laboratory Head
Hitoshi OKAMOTO (M.D., Ph.D.)
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Research Areas

  1. Investigating the role of the evolutionary conserved limbic circuit within vertebrates.
    We investigate the role of neural circuits that control the selection and execution of emotional behaviors. We study fish and rodents using various methods including the genetics, molecular and cell biology and physiology. In mammalian telencephalon, the cortico-basal ganglia circuit is thought to be involved in selection of the behavioral programs (Figure A). External physical information and related emotional information enter the cortico basal ganglia circuit via the hippocampus and amygdala, respectively, and modulate this circuit to establish ensembles of neurons encoding various behavioral programs (Figure A). However, it is still unclear how a particular ensemble of neurons becomes selected through this neural circuit.
    Zebrafish (teleosts) have the simplest neural system in the vertebrates. By the movement of the neural tube called eversion, the hippocampus and amygdala in fish become located in the medial and lateral part of the telencephalon, respectively (Figure B), showing the inside out position with respect to that of mammals. Furthermore, it has been recently shown that the zebrafish telencephalon may contain the cortico-basal ganglia circuit where the behavioral programs become stored. Zebrafish brain is so small that we can analyze the neural activities of the entire cortico-basal ganglia circuit by the calcium imaging. By combining with the optogenetics to interfere the activity of the cortico-basal ganglia circuit, we believe that the common neural mechanisms between fish and mammals which underly the establishment of the memory for the behavioral program will be unveiled.
  2. Exploring the role of habenula in emotional behaviors.
    We also focus on the habenula, a nucleus located in the dorsal midbrain. Mammalian habenula consists of the medial and lateral nucleus (Figure C, E), which control directly and indirectly dopaminergic neurons in the ventral tegmental area and serotonergic neurons in the Raphe, respectively (Figure C, D). The medial and lateral parts of the habenula in mammals correspond to the dorsal and ventral habenula in fish, respectively (Figure E), and the connectivity of each subnucleus is well conserved between fish and mammals (Figure D, E). We are trying to reveal the role of this well conserved habenula circuit in the control of emotional behaviors. In deed, when the zebrafish dorsal habenula is inactivated by the neurotoxin, fish tend to select the freezing instead of the agitating behavior in the cued-fear conditioning (Figure F). We study the role of the habenula in switching of the emotional behaviors, the adaptive fear learning, the aggressiveness or the social dominant-subordinate relationships, using zebrafish, rats and mice.
  3. Studying the mechanism of the sensory neuron development and adult neurogenesis.
    We study the role of Trk signaling pathway in the sensory neuron development and adult neurogenesis using zebrafish and mice.

Research Subject

  1. Investigating the role of the evolutionary conserved limbic circuit within vertebrates.
  2. Exploring the role of habenula in emotional behaviors.
  3. Studying the mechanism of the sensory neuron development and adult neurogenesis.

Related links

  1. RIKEN Brain Science Institute Website_Laboratories PageNew Window
  2. Individual Website Laboratory PageNew Window
  3. National BioResource Project ZEBRA FISH PageNew Window

Press release

January 27, 2011
Mechanism uncovered explaining why neuronal stem cell mitosis is restricted to only the ventricle side
October 11, 2010
Study identifies neural pathways governing switching of fear responses in the zebrafish

RIKEN RESEARCH

April 28, 2011
Following directions
A key regulator of nervous system development works by blocking a signaling protein with multiple roles in stem cell maturationNew Window
December 17, 2010
Fish frozen in fear
Fear responses of zebrafish are controlled by brain structures of previously unknown functionNew Window
March 23, 2007
Timing is everything
New work sheds light on the processes determining brain asymmetryNew Window

List of Selected Publications

  1. Agetsuma, M., Aizawa, H., Aoki, T., Nakayama, R., Takahoko, M., Goto, M., Sassa, T., Amo, R., Shiraki, T., Kawakami, K., Hosoya, T., Higashijima, S. and Okamoto, H.:
    "The habenula is crucial for experience-dependent modification of fear responses in zebrafish"
    Nature Neuroscience, 13(11), 1354-1356 (2010)
  2. Ohata, S., Aoki, R., Kinoshita, S., Yamaguchi, M., Tsuruoka-Kinoshita, S., Tanaka, H., Wada, H., Watabe, S., Masai, I. and Okamoto, H.:
    "Dual roles of notch in regulation of apically restricted mitosis and apicobasal polarity of neuroepithelial cells"
    Neuron, 69, 215-230 (2011)
  3. Amo, R., Aizawa, H., Takahoko, M., Kobayashi, M., Takahashi, R., Aoki, T. and Okamoto, H.:
    "Identification of the zebrafish ventral habenula as a homolog of the mammalian lateral habenula"
    The Journal of Neuroscience, 30(4), 1566-1574 (2010)
  4. Ohata, S., Kinoshita, S., Aoki, R., Tanaka H., Wada H., Tsuruoka, S., Tsuboi, T., Watabe, S. and Okamoto, H.:
    "Neuroepithelial cells require fucosylated glycans to guide the migration of vagus motor neuron progenitors in the developing zebrafish hindbrain"
    Development, 136, 1653-1663(2009)
  5. Aizawa, H., Goto, M., Sato T., and Okamoto. H.:
    "Temporally regulated asymmetric neurogenesis causes left-right difference in the zebrafish habenular structures"
    Developmental Cell, 12, 87-98 (2007)
  6. Wada, H., Tanaka, H., Nakayama S., Iwasaki, M., and Okamoto. H.:
    "Frizzled3a and Celsr2 function in the neuroepithelium to regulate migration of facial motor neurons in the developing zebrafish hindbrain"
    Development, 133, 4749-4759 (2006)
  7. Aizawa,H., Bianco, I.H., Hamaoka, T., Miyashita, T., Uemura,O., Concha, M.L., Russell, Wilson, S.W., and Okamoto, H.:
    "Laterotopic Representation of Left-Right Information onto the Dorso-Ventral Axis of a Zebrafish Midbrain Target Nucleus"
    Current Biology, 15, 238-243 (2005).
  8. Wada, H., Iwasaki, M., Sato, T., Masai, I., Nishiwaki, Y., Tanaka, H., Sato, A., Nojima, Y., and Okamoto, H.:
    "Dual roles of zygotic and maternal Scribble1 in neural migration and convergent extension movements in zebrafish embryos"
    Development. 132, 2273-2285 (2005).
  9. Ando, H., Furuta, T., Tsien., R.Y., and Okamoto., H.:
    "Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos."
    nature genetics, 28, 317-325(2001).
  10. Segawa, H.., Miyashita, T., Hirate, Y., Higashijima, S., Chino, N., Uyemura, K., Kikuchi, Y., and Okamoto, H.:
    "Functional repression of Islet-2 by disruption of complex with Ldb impairs peripheral axonal outgrowth in embryonic zebrafish"
    Neuron, 30, 423-436(2001).

Members

Principal Investigator

Hitoshi OKAMOTO
Laboratory Head

Members

Hisaya KAKINUMA
Research Scientist
Douglas Simon CAMPBELL
Research Scientist
Masae KINOSHITA
Research Scientist
Ming-Yi CHOU
Research Scientist
Miho MATSUMATA
Research Scientist
Felipe Andres FREDES TOLORZA
Research Scientist
Shin YANAGIHARA
Research Scientist
Ryunosuke AMO
Research Scientist
Tazu AOKI
Special Postdoctoral Researcher
Makoto AOKI
Research Associate
Ryo AOKI
Student Trainee
Hidefumi NISHIDA
Student Trainee
Tomoya NAKAI
Student Trainee
Takefumi OHKI
Student Trainee
Mai IWASAKI
Student Trainee
Megumi KOBAYASHI
Technical Staff I
Atsuko SHIMADA
Technical Staff I/Assistant
Kawori EIZUMI
Technical Staff I
Masako YAMAZAKI
Technical Staff II
Hidenori AIZAWA
Senior Visiting Scientist
Akiko ARATA
Visiting Scientist
Masakazu AGETSUMA
Visiting Scientist
Shinya OHATA
Visiting Scientist
Hironori WADA
Visiting Scientist
Hideki ANDO
Visiting Scientist
Hideomi TANAKA
Visiting Scientist
Takashi TSUBOI
Visiting Scientist
Teiichi FURUICHI
Visiting Scientist
Motoko WATANABE
Part-time Staff