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Nat Commun. 2014;5:3337. doi: 10.1038/ncomms4337.

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

Author information

  • 11] 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.
  • 2KAN Research Institute Inc., 3F, Kobe MI R&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
  • 3Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
  • 41] KAN Research Institute Inc., 3F, Kobe MI R&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan [2].
  • 51] 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.
  • 6Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3026, USA.
  • 7Department 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.
  • 8Vanderbilt 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.
  • 9Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
  • 101] 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.
  • 111] 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.
  • 121] 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.

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.

PMID:
24535035
DOI:
10.1038/ncomms4337
[PubMed - indexed for MEDLINE]
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