小脑浦肯野细胞祖细胞向GABA能中间神经元祖细胞的时间身份转变。
Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum.
作者信息
Seto Yusuke, Nakatani Tomoya, Masuyama Norihisa, Taya Shinichiro, Kumai Minoru, Minaki Yasuko, Hamaguchi Akiko, Inoue Yukiko U, Inoue Takayoshi, Miyashita Satoshi, Fujiyama Tomoyuki, Yamada Mayumi, Chapman Heather, Campbell Kenneth, Magnuson Mark A, Wright Christopher V, Kawaguchi Yoshiya, Ikenaka Kazuhiro, Takebayashi Hirohide, Ishiwata Shin'ichi, Ono Yuichi, Hoshino Mikio
机构信息
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.
KAN Research Institute Inc., 3F, Kobe MI R&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
出版信息
Nat Commun. 2014;5:3337. doi: 10.1038/ncomms4337.
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.
在小脑内，所有γ-氨基丁酸能神经元均由表达Ptf1a的脑室区（Ptf1a区域）产生。然而，产生不同类型γ-氨基丁酸能神经元的机制仍不清楚。在此，我们展示了小脑中不同γ-氨基丁酸能神经元祖细胞的时间调控。在早期的Ptf1a区域内，我们发现了两个亚群；分别位于背侧和腹侧的祖细胞，它们分别表达Olig2和Gsx1。谱系追踪显示，前者是唯一的浦肯野细胞祖细胞（PCP），后者是Pax2阳性中间神经元祖细胞（PIP）。随着发育的进行，PCP从腹侧到背侧逐渐转变为PIP。在Gsx1以及Olig1/2功能获得和功能缺失突变体中，我们观察到在不适当的发育阶段PCP向PIP的异常转变。我们的研究结果表明，小脑γ-氨基丁酸能神经元祖细胞从PCP到PIP的时间特性转变受到Olig2的负调控和Gsx1的正调控，这有助于理解神经元祖细胞特性的时间控制。
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