Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum
Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum
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DOI：
10.1016/j.neuron.2005.06.007
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发表时间：
2005-07-21
期刊：
影响因子：
16.2
通讯作者：
Nabeshima, YI
中科院分区：
文献类型：
--
作者：
Hoshino, M;Nakamura, S;Nabeshima, YI
尚不清楚谷氨酸能 - gaba能神经元亚型规范的分子机制尚不清楚。在这里，我们描述了一个小脑突变体小脑，该突变体缺乏成年人的整个小脑皮层。突变大脑的主要缺陷是对小脑心室区（VZ）的GABA能神经元产生的特异性抑制作用，导致发育过程中外部生发层，蓬托和橄榄核的次生和完全损失。我们确定了负责任的基因PTF1A，其表达在小脑VZ中失去，但在小脑的胰腺中保持了。谱系跟踪表明，在小脑VZ中存在两种类型的神经前体：表达Ptf1a的表达和-NONEXPRESS PRECSURS，它们分别产生了GABAergic和Gabaeragic和Glutamatorgic神经元。将PTF1A引入背脑脑脑中的谷氨酸能神经元前体中，产生了具有代表性的形态和迁移特征的GABA能神经元。我们的结果表明，PTF1A参与驱动神经前体以区分小脑的GABA能神经元。
The molecular machinery governing glutamatergic-GABAergic neuronal subtype specification is unclear. Here we describe a cerebellar mutant, cerebelless, which lacks the entire cerebellar cortex in adults. The primary defect of the mutant brains was a specific inhibition of GABAergic neuron production from the cerebellar ventricular zone (VZ), resulting in secondary and complete loss of external germinal layer, pontine, and olivary nuclei during development. We identified the responsible gene, Ptf1a, whose expression was lost in the cerebellar VZ but was maintained in the pancreas in cerebelless. Lineage tracing revealed that two types of neural precursors exist in the cerebellar VZ: Ptf1a-expressing and -nonexpressing precursors, which generate GABAergic and glutamatergic neurons, respectively. Introduction of Ptf1a into glutamatergic neuron precursors in the dorsal telencephalon generated GABAergic neurons with representative morphological and migratory features. Our results suggest that Ptf1a is involved in driving neural precursors to differentiate into GABAergic neurons in the cerebellum.