Neuronal basic helix-loop-helix proteins (NEX and BETA2/Neuro D) regulate terminal granule cell differentiation in the hippocampus
Neuronal basic helix-loop-helix proteins (NEX and BETA2/Neuro D) regulate terminal granule cell differentiation in the hippocampus
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DOI：
10.1523/jneurosci.20-10-03714.2000
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发表时间：
2000-05-15
影响因子：
5.3
通讯作者：
Nave, KA
中科院分区：
文献类型：
--
作者：
Schwab, MH;Bartholomae, A;Nave, KA
转录因子神经元螺旋-环-螺旋蛋白(NEX)/哺乳动物无性同源蛋白2(Math-2)、β-2/神经元决定因子(NeuroD)和神经D相关因子(NDRF)/NeuroD2组成了一个在发育中的前脑高度重叠表达的果蝇无性相关碱性螺旋-环-螺旋(BHLH)蛋白家族。将mRNA注入非洲爪哇卵母细胞后，Beta2/Neurod和NDRF将外胚层细胞转化为神经元的能力表明，它在决定神经细胞命运方面发挥了作用。然而，神经元中的bHLH基因主要在中枢神经系统神经元中转录，这些神经元是完全承诺的。在这里，我们分析了缺乏Beta2/Neurod和NEX*Beta2/Neurod双突变的小鼠的缺陷，证明了bHLH蛋白在体内是终末神经元分化所必需的。最引人注目的是，齿状回的颗粒细胞生成但不成熟，缺乏正常的钠电流，并显示很少的树突树枝。长期的海马片培养显示内嗅觉和连合/联合投射的继发性改变。初级发育停滞似乎仅限于颗粒细胞，在颗粒细胞中，涉及所有三个神经元bHLH基因的自动调节系统已经失败。
The transcription factors neuronal helix-loop-helix protein (NEX)/mammalian atonal homolog 2 (Math-2), BETA2/neuronal determination factor (NeuroD), and NeuroD-related factor (NDRF)/NeuroD2 comprise a family of Drosophila atonal-related basic helix-loop-helix (bHLH) proteins with highly overlapping expression in the developing forebrain. The ability of BETA2/NeuroD and NDRF to convert ectodermal cells into neurons after mRNA injection into Xenopus oocytes suggested a role in specifying neuronal cell fate. However, neuronal bHLH genes are largely transcribed in CNS neurons, which are fully committed. Here we analyze a defect in mice lacking BETA2/NeuroD, and in NEX*BETA2/NeuroD double mutants, demonstrating that bHLH proteins are required in vivo for terminal neuronal differentiation. Most strikingly, presumptive granule cells of the dentate gyrus are generated but fail to mature, lack normal sodium currents, and show little dendritic arborization. Long-term hippocampal slice cultures demonstrate secondary alterations of entorhinal and commissural/associational projections. The primary developmental arrest appears to be restricted to granule cells in which an autoregulatory system involving all three neuronal bHLH genes has failed.