Neurogenin2 directs granule neuroblast production and amplification while NeuroD1 specifies neuronal fate during hippocampal neurogenesis.
Neurogenin2 directs granule neuroblast production and amplification while NeuroD1 specifies neuronal fate during hippocampal neurogenesis.
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DOI：
10.1371/journal.pone.0004779
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Brundin P
中科院分区：
文献类型：
--
作者：
Roybon L;Hjalt T;Stott S;Guillemot F;Li JY;Brundin P
海马齿状回颗粒神经元的特化和分化需要内在和外在分子在时间和空间上的协调作用。碱性螺旋-环-螺旋转录因子神经生成素2（Ngn 2）和NeuroD 1是这些过程中的关键调节因子。基于现有的分类，我们分析了海马神经发生过程中发生的分子事件，主要集中在幼年动物。我们发现Ngn 2由晚期2a型扩增祖细胞瞬时表达。Ngn 2后代成熟为海马颗粒神经元。有趣的是，在发育的早期阶段Ngn 2的丢失导致神经发生的强烈减少，但不会干扰颗粒神经元本身的成熟。我们发现Ngn 2的作用是维持祖细胞处于未分化状态，允许它们在NeuroD 1诱导后成熟为颗粒神经元之前扩增。当我们在体内过表达Ngn 2和NeuroD1时，我们发现NeuroD1表现出比Ngn 2更明显的神经元诱导作用，导致颗粒神经元定型。最后，我们观察到，在啮齿动物海马神经发生的转录控制过程中表达的所有标记物也存在于人类海马中。两者合计，我们证明了Ngn 2和NeuroD1在控制神经元的承诺和海马颗粒神经母细胞的形成，无论是在胚胎发育和出生后的海马颗粒神经发生的关键作用。
The specification and differentiation of dentate gyrus granule neurons in the hippocampus require temporally and spatially coordinated actions of both intrinsic and extrinsic molecules. The basic helix-loop-helix transcription factor Neurogenin2 (Ngn2) and NeuroD1 are key regulators in these processes. Based on existing classification, we analyzed the molecular events occurring during hippocampal neurogenesis, primarily focusing on juvenile animals. We found that Ngn2 is transiently expressed by late type-2a amplifying progenitors. The Ngn2 progenies mature into hippocampal granule neurons. Interestingly, the loss of Ngn2 at early stages of development leads to a robust reduction in neurogenesis, but does not disturb granule neuron maturation per se. We found that the role of Ngn2 is to maintain progenitors in an undifferentiated state, allowing them to amplify prior to their maturation into granule neurons upon NeuroD1 induction. When we overexpressed Ngn2 and NeuroD1 in vivo, we found NeuroD1 to exhibit a more pronounced neuron-inductive effect, leading to granule neuron commitment, than that displayed by Ngn2. Finally, we observed that all markers expressed during the transcriptional control of hippocampal neurogenesis in rodents are also present in the human hippocampus. Taken together, we demonstrate a critical role of for Ngn2 and NeuroD1 in controlling neuronal commitment and hippocampal granule neuroblast formation, both during embryonic development and in post-natal hippocampal granule neurogenesis.
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影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
DOI：
10.1073/pnas.96.10.5768
发表时间：
1999-05-11
影响因子：
11.1
作者：
Kornack, DR;Rakic, P
通讯作者：
Rakic, P
影响因子：
2.5
作者：
Kronenberg, G;Reuter, K;Kempermann, G
通讯作者：
Kempermann, G
影响因子：
21.3
作者：
Konno, Daijiro;Shioi, Go;Matsuzaki, Fumio
通讯作者：
Matsuzaki, Fumio
影响因子：
4.6
作者：
Andersson, E;Jensen, JB;Björklund, A
通讯作者：
Björklund, A