Notch1 is required for neuronal and glial differentiation in the cerebellum.
Notch1 is required for neuronal and glial differentiation in the cerebellum.
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DOI：
10.1242/dev.129.2.373
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发表时间：
2002-01
期刊：
影响因子：
4.6
通讯作者：
S. Luetolf;F. Radtke;M. Aguet;U. Suter;V. Taylor
中科院分区：
文献类型：
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作者：
S. Luetolf;F. Radtke;M. Aguet;U. Suter;V. Taylor
脊椎动物中枢神经系统（CNS）中指导祖细胞命运和分化的机制知之甚少。功能获得实验表明，Notch信号参与哺乳动物神经发生的早期阶段。基于Notch 1在脊椎动物中枢神经系统的假定祖细胞中的表达，我们直接研究了Notch 1在哺乳动物脑发育中的作用。使用条件性基因消融，我们发现Notch 1的丢失导致中脑-后脑区域神经管的神经上皮细胞过早发生神经发生。Notch 1缺陷细胞不能完全分化，而是通过凋亡消除，导致成年小脑中神经元数量减少。我们还分析了Notch 1消融对体内胶质细胞生成的影响。我们的研究结果表明，Notch 1是所需的神经元和胶质细胞的形成和调制小脑神经上皮内的神经发生的发病。
The mechanisms that guide progenitor cell fate and differentiation in the vertebrate central nervous system (CNS) are poorly understood. Gain-of-function experiments suggest that Notch signaling is involved in the early stages of mammalian neurogenesis. On the basis of the expression of Notch1 by putative progenitor cells of the vertebrate CNS, we have addressed directly the role of Notch1 in the development of the mammalian brain. Using conditional gene ablation, we show that loss of Notch1 results in premature onset of neurogenesis by neuroepithelial cells of the midbrain-hindbrain region of the neural tube. Notch1-deficient cells do not complete differentiation but are eliminated by apoptosis, resulting in a reduced number of neurons in the adult cerebellum. We have also analyzed the effects of Notch1 ablation on gliogenesis in vivo. Our results show that Notch1 is required for both neuron and glia formation and modulates the onset of neurogenesis within the cerebellar neuroepithelium.