Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum

Yusuke Seto, Tomoya Nakatani, Norihisa Masuyama, Shinichiro Taya, Minoru Kumai, Yasuko Minaki, Akiko Hamaguchi, Yukiko U. Inoue, Takayoshi Inoue, Satoshi Miyashita, Tomoyuki Fujiyama, Mayumi Yamada, Heather Chapman, Kenneth Campbell, Mark A. Magnuson, Christopher V. Wright, Yoshiya Kawaguchi, Kazuhiro Ikenaka, Hirohide Takebayashi, Shin’ichi Ishiwata, Yuichi Ono () and Mikio Hoshino ()
Additional contact information
Yusuke Seto: National Institute of Neuroscience, NCNP
Tomoya Nakatani: KAN Research Institute Inc., 3F, Kobe MI R&D Center
Norihisa Masuyama: National Institute of Neuroscience, NCNP
Shinichiro Taya: National Institute of Neuroscience, NCNP
Minoru Kumai: KAN Research Institute Inc., 3F, Kobe MI R&D Center
Yasuko Minaki: KAN Research Institute Inc., 3F, Kobe MI R&D Center
Akiko Hamaguchi: KAN Research Institute Inc., 3F, Kobe MI R&D Center
Yukiko U. Inoue: National Institute of Neuroscience, NCNP
Takayoshi Inoue: National Institute of Neuroscience, NCNP
Satoshi Miyashita: National Institute of Neuroscience, NCNP
Tomoyuki Fujiyama: National Institute of Neuroscience, NCNP
Mayumi Yamada: National Institute of Neuroscience, NCNP
Heather Chapman: Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine
Kenneth Campbell: Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine
Mark A. Magnuson: Vanderbilt University School of Medicine
Christopher V. Wright: Vanderbilt University Program in Developmental Biology, Vanderbilt University Medical Center
Yoshiya Kawaguchi: Center for iPS Cell Research and Application, Kyoto University
Kazuhiro Ikenaka: National Institute for Physiological Sciences
Hirohide Takebayashi: National Institute for Physiological Sciences
Shin’ichi Ishiwata: Major in Integrative Bioscience and Biomedical Engineering, Faculty of Science and Engineering, Waseda University
Yuichi Ono: KAN Research Institute Inc., 3F, Kobe MI R&D Center
Mikio Hoshino: National Institute of Neuroscience, NCNP

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract In the cerebellum, all GABAergic neurons are generated from the Ptf1a-expressing ventricular zone (Ptf1a domain). However, the machinery to produce different types of GABAergic neurons remains elusive. Here we show temporal regulation of distinct GABAergic neuron progenitors in the cerebellum. Within the Ptf1a domain at early stages, we find two subpopulations; dorsally and ventrally located progenitors that express Olig2 and Gsx1, respectively. Lineage tracing reveals the former are exclusively Purkinje cell progenitors (PCPs) and the latter Pax2-positive interneuron progenitors (PIPs). As development proceeds, PCPs gradually become PIPs starting from ventral to dorsal. In gain- and loss-of-function mutants for Gsx1 and Olig1/2, we observe abnormal transitioning from PCPs to PIPs at inappropriate developmental stages. Our findings suggest that the temporal identity transition of cerebellar GABAergic neuron progenitors from PCPs to PIPs is negatively regulated by Olig2 and positively by Gsx1, and contributes to understanding temporal control of neuronal progenitor identities.

Date: 2014
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DOI: 10.1038/ncomms4337

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