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

Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum.
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DOI:
10.1038/ncomms4337
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发表时间:
2014
影响因子:
16.6
通讯作者:
Hoshino M
Hoshino M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Seto Y;Nakatani T;Masuyama N;Taya S;Kumai M;Minaki Y;Hamaguchi A;Inoue YU;Inoue T;Miyashita S;Fujiyama T;Yamada M;Chapman H;Campbell K;Magnuson MA;Wright CV;Kawaguchi Y;Ikenaka K;Takebayashi H;Ishiwata S;Ono Y;Hoshino M

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在小脑中,所有gaba能神经元都来自表达Ptf1a的心室区(Ptf1a结构域)。然而,产生不同类型gaba能神经元的机制仍然是难以捉摸的。在这里,我们展示了小脑中不同gaba能神经元祖细胞的时间调节。在Ptf1a结构域的早期阶段,我们发现了两个亚群;分别表达Olig2和Gsx1的背侧和腹侧祖细胞。谱系追踪显示前者仅为浦肯野细胞祖细胞(pcp),后者为pax2阳性中间神经元祖细胞(PIPs)。随着发育的进行,pcp从腹侧到背侧逐渐变成pip。在Gsx1和Olig1/2的功能获得和功能丧失突变体中,我们观察到在不适当的发育阶段从pcp到PIPs的异常过渡。我们的研究结果表明,小脑gaba能神经元祖细胞从pcp到PIPs的时间身份转换受Olig2的负调控,而Gsx1的正调控,这有助于理解神经元祖细胞身份的时间控制。
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.
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