Laboratory for Developmental Gene Regulation

For its relatively short generation time and simple body structure, zebrafish embryos are the ideal vertebrate model organisms in which both cell biological and genetic manipulations are amenable for the study of cognitive function as well as neural differentiation.
Making extensive use of these advantages, we focus on the habenular circuitry to reveal the brain mechanisms which controls emotional behavior conserved across vertebrates. Using the transgenic technology, we have recently identified the left-right difference in the habenular neural circuit that connects the limbic forebrain and the midbrain. We are now trying to understand the biological significance of this asymmetric neural circuit in control of zebrafish behavior. Furthermore, we are now extending our research to investigate the function of the habenula in regulation of emotion and memory by intensive use of genetic manipulation and electrophysiological analysis both in zebrafish and mammals.
We also continue our research initiated from the analyses of zebrafish developmental mutants. This study is now revealing the key characteristics of the neuroepitehlial cells, i.e. why they divide and differentiate only in the ventricular zone.

Research Subjects

• Functional analysis of the habenula in zebrafish in emotional behaviors
• Visualization and manipulation of the neural activities in evolutionarily conserved telecephalic structures in zebrafish accompanying emotional or goal-directed behaviors
• Study of the functional role of the mammalian habenula in formation of memory and fear
• Study on the coordinated regulation of the neural development by the neuroepithelial polarity factors

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).