Origins and control of the differentiation of inhibitory interneurons and glia in the cerebellum
Origins and control of the differentiation of inhibitory interneurons and glia in the cerebellum
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DOI：
10.1016/j.ydbio.2009.02.008
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发表时间：
2009-04-15
影响因子：
2.7
通讯作者：
Wassef, Marion
中科院分区：
文献类型：
--
作者：
Grimaldi, Piercesare;Parras, Carlos;Wassef, Marion
小脑GABA能中间神经元和神经胶质细胞起源于从脑室神经上皮细胞分层并在预期的白色物质中增殖的祖细胞。尽管这群祖细胞作为一个整体是多能的，克隆分析表明，不同的谱系已经分离在出生后的发展和鲜为人知的机制，规范和这些小脑类型的分化在早期阶段。在这里，我们调查的作用Ascl 1在发展中的抑制性中间神经元和胶质细胞在小脑。该基因由成熟的少突胶质细胞和GABA能中间神经元表达，并且是产生适当数量的这些细胞所必需的，这些细胞在Ascl 1（-/-）小鼠小脑中严重减少。然而，这两个谱系是不相关的，大多数的少突胶质细胞实际上来自小脑外来源。靶向电穿孔的Ascl 1表达载体心室神经上皮祖细胞增强生产的中间神经元和完全抑制星形胶质细胞的分化，而Ascl 1功能的损失对两种细胞类型有相反的影响。我们的研究结果表明，Ascl 1指导心室神经上皮祖细胞对抑制性中间神经元的命运，并限制他们的能力，分化沿着星形胶质细胞谱系。(C)2009 Elsevier Inc. All rights reserved.
Cerebellar GABAergic interneurons and glia originate from progenitors that delaminate from the ventricular neuroepithelium and proliferate in the prospective white matter. Even though this population of progenitor cells is multipotent as a whole, clonal analysis indicates that different lineages are already separated during postnatal development and little is known about the mechanisms that regulate the specification and differentiation of these cerebellar types at earlier stages. Here, we investigate the role of Ascl1 in the development of inhibitory interneurons and glial cells in the cerebellum. This gene is expressed by maturing oligodendrocytes and GABAergic interneurons and is required for the production of appropriate quantities of these cells, which are severely reduced in Ascl1(-/-) mouse cerebella. Nevertheless, the two lineages are not related and the majority of oligodendrocytes populating the developing cerebellum actually derive from extracerebellar sources. Targeted electroporation of Ascl1-expression vectors to ventricular neuroepithelium progenitors enhances the production of interneurons and completely suppresses astrocytic differentiation, whereas loss of Ascl1 function has opposite effects on both cell types. Our results indicate that Ascl1 directs ventricular neuroepithelium progenitors towards inhibitory interneuron fate and restricts their ability to differentiate along the astroglial lineage. (C) 2009 Elsevier Inc. All rights reserved.