NeuroD2 is necessary for development and survival of central nervous system neurons
NeuroD2 is necessary for development and survival of central nervous system neurons
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DOI：
10.1006/dbio.2001.0245
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发表时间：
2001-06-01
影响因子：
2.7
通讯作者：
Tapscott, SJ
中科院分区：
文献类型：
--
作者：
Olson, JM;Asakura, A;Tapscott, SJ
NeuroD2 足以诱导非神经元细胞的细胞周期停滞和神经源性分化。为了确定该 bHLH 转录因子是否是正常大脑发育所必需的，我们使用同源重组用 β-半乳糖苷酶报告基因替换 NeuroD2 编码区。 NeuroD2 基因在中枢神经系统的一部分神经元中表达报告基因，包括新皮质、海马和小脑的神经元。 NeuroD2(-/-)小鼠直到第14天左右才表现出正常发育，此时它们开始表现出共济失调和发育迟缓。表达neuroD2的大脑区域比正常情况要小，并且细胞凋亡率更高，neuroD2缺失小鼠的小脑表达编码支持小脑颗粒细胞存活的蛋白质的基因水平降低，包括脑源性神经营养因子（BDNF）。neuroDe（-/-）小鼠的小脑颗粒细胞中BDNF水平降低和细胞凋亡率升高表明，neuroD2对于中枢神经系统神经元特定群体的生存是必需的。对细胞周期调节和神经元分化的已知影响。 (C) 2001 年学术出版社。
NeuroD2 is sufficient to induce cell cycle arrest and neurogenic differentiation in nonneuronal cells. To determine whether this bHLH transcription factor was necessary for normal brain development, we used homologous recombination to replace the neuroD2 coding region with a p-galactosidase reporter gene. The neuroD2 gene expressed the reporter in a subset of neurons in the central nervous system, including in neurons of the neocortex and hippocampus and cerebellum. NeuroD2(-/-)mice showed normal development until about day P14, when they began exhibiting ataxia and failure to thrive. Brain areas that expressed neuroD2 were smaller than normal and showed higher rates of apoptosis, Cerebella of neuroD2-null mice expressed reduced levels of genes encoding proteins that support cerebellar granule cell survival, including brain-derived neurotrophic factor (BDNF), Decreased levels of BDNF and higher rates of apoptosis in cerebellar granule cells of neuroDe(-/-)mice indicate that neuroD2 is necessary for the survival of specific populations of central nervous system neurons in addition to its known effects on cell cycle regulation and neuronal differentiation. (C) 2001 Academic Press.