Department of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, The University of Tokyo
Neural Development, Neural Stem/Progenitor Cells, Epigenetics, Signal Transduction
A fundamental question in understanding tissue development is how resident stem cells or multipotent progenitors give rise to the various cell types in appropriate numbers and at the right locations to achieve tissue organization. Our laboratory has been studying the mechanisms and logic that underlie the regulation of neural stem/progenitor cell fate both during embryonic brain development and in the adult brain. Our current research foci include the genetic and epigenetic regulation of neural stem/progenitor cell fate and neuronal maturation, the genesis and maintenance of adult neural stem cells, and the relevance of neural stem/progenitor cell dysregulation in neurodevelopmental disorders such as autism spectrum disorders.
Furutachi, S., Miya, H., Watanabe, T., Kawai, H., Yamasaki, N., Harada, Y., Imayoshi, I., Nelson, M., Nakayama, KI., Hirabayashi, Y., and Gotoh, Y. (2015) Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells. Nat. Neurosci. 18, 657-665.
Kishi, Y., Fujii, Y., Hirabayashi, Y. and Gotoh, Y. (2012) HMGA proteins regulate global chromatin state and the neurogenic potential in neocortical precursor cells. Nat. Neurosci. 15, 1127-1133.
Hirabayashi, Y., Suzki, N., Tsuboi, M., Endo, T.A., Toyoda, T., Shinga, J., Koseki, H., Vidal, M. and Gotoh, Y. (2009) Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition. Neuron 63, 600-613.
Ichijo, H., Nishida, E., Irie, K., ten Dijke, P., Saitoh, M., Moriguchi, T., Takagi, M., Matsumoto, K., Miyazono, K. and Gotoh, Y. (1997) Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 275, 90-94.
Gotoh, Y., Nishida, E., Matsuda, S., Shiina, N., Kosako, H., Shiokawa, K., Akiyama, T., Ohta, K. & Sakai, H. (1991) In vitro effects on microtubule dynamics of purified Xenopus M phase-activated MAP kinase. Nature 349, 251-254.
Gotoh, Y., Nishida, E., Yamashita, T., Hoshi, M., Kawakami, M. & Sakai, H. (1990) MAP kinase activated by nerve growth factor and epidermal growth factor in PC12 cells. Identity with the mitogen-activated MAP kinase of fibroblastic cells. Eur. J. Biochem. 193, 661-669.
As a graduate student at the University of Tokyo and later as an Assistant Professor in Kyoto University where I led a group with Eisuke Nishida, our group purified and cloned the vertebrate MAP kinase (Erk) and its activator, MAP kinase kinase (Mek). I became fascinated by the beauty of the cell fate decision where, even using the same MAPK pathway, a cell can precisely decide whether it should proliferate or differentiate. After spending a few years in Jonathan Cooper’s laboratory in Seattle and Michael Greenberg’s laboratory in Boston where I learned the basics of brain development, I started a laboratory investigating neural stem/progenitor cell fate at the University of Tokyo at the Institute of Molecular and Cellular Biosciences in 2000. I was later appointed as a Professor at the same institute in 2005 and then in the Department of Pharmaceutical Sciences of the University of Tokyo in 2014.