title: Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum.
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.
authors.affiliation: 1] Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan [2] Department of Physics, Major in Integrative Bioscience and Biomedical Engineering, Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Seto
authors.affiliation: KAN Research Institute Inc., 3F, Kobe MI R&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakatani
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Masuyama
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Taya
authors.affiliation: KAN Research Institute Inc., 3F, Kobe MI R&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kumai
authors.affiliation: 1] KAN Research Institute Inc., 3F, Kobe MI R&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan [2].
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Minaki
authors.affiliation: KAN Research Institute Inc., 3F, Kobe MI R&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hamaguchi
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Yukiko U
authors.initials: YU
authors.lastname: Inoue
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: 1] Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan [2] Department of Electrical Engineering and Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyashita
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujiyama
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3026, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Chapman
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3026, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Campbell
authors.affiliation: Department of Molecular Physiology and Biophysics and Center for Stem Cell Biology, Vanderbilt University School of Medicine, 2213 Garland Avenue, 9465 MRB IV, Nashville, Tennessee 37232-0494, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Magnuson
authors.affiliation: Vanderbilt University Program in Developmental Biology, Department of Cell and Developmental Biology, Vanderbilt University Medical Center, 2213 Garland Avenue, 9465 MRB IV, Nashville, Tennessee 37232-0494, USA.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Wright
authors.affiliation: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: 1] Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan [2] Department of Physiological Sciences, School of Life Sciences, Graduate University for Advanced Studies, Shonan Village, Hayama, Kanagawa 240-0193, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka
authors.affiliation: 1] Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan [2] Department of Physiological Sciences, School of Life Sciences, Graduate University for Advanced Studies, Shonan Village, Hayama, Kanagawa 240-0193, Japan [3] Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi, Chuo-ku, Niigata 951-8510, Japan.
authors.forename: Hirohide
authors.initials: H
authors.lastname: Takebayashi
authors.affiliation: 1] Department of Physics, Major in Integrative Bioscience and Biomedical Engineering, Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan [2] Waseda Bioscience Research Institute in Singapore, Waseda University, 11 Biopolis Way, #05-01/02, Helios, Singapore 138667, Republic of Singapore.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Ishiwata
authors.affiliation: KAN Research Institute Inc., 3F, Kobe MI R&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Hoshino
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D059330:GABAergic Neurons / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D014157:Transcription Factors; C512773:Olig2 protein, mouse; C062602:transcription factor PTF1