The on/off of Pax6 controls the tempo of neuronal differentiation in the developing spinal cord
The on/off of Pax6 controls the tempo of neuronal differentiation in the developing spinal cord
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DOI：
10.1016/j.ydbio.2007.02.012
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发表时间：
2007-05-15
影响因子：
2.7
通讯作者：
Pituello, Fabienne
中科院分区：
文献类型：
--
作者：
Bel-Vialar, Sophie;Medevielle, Francois;Pituello, Fabienne
在神经发生过程中，复杂的基因网络依次控制神经元的分化。在神经管中，Pax6（一种含有配对盒的基因）的表达恰好先于第一个有丝分裂后神经元的出现。到目前为止，它在脊髓中的唯一报道功能是指定神经元的子集。在这里，我们解决其可能的功能，在控制之间的平衡，神经祖细胞的增殖和承诺。我们报告说，增加Pax6水平是足以推动神经祖细胞对细胞周期退出和神经元承诺通过神经生成素2（Ngn 2）上调。然而，维持Pax6（On）的神经元前体不能进行神经元分化。相反，在这些前体中关闭Pax6功能足以引起过早分化，并且分化的神经元的数量取决于Pax6蛋白的量。此外，我们发现Pax6表达涉及Ngn 2的负反馈调节，这种抑制对于Ngn 2的前神经活性至关重要。我们提出了一个模型，其中Pax 6活性水平首先决定给定祖细胞离开细胞周期的时刻，其次决定选定神经元前体不可逆分化的时刻。(c)2007年爱思唯尔公司All rights reserved.
During neurogenesis, complex networks of genes act sequentially to control neuronal differentiation. In the neural tube, the expression of Pax6, a paired-box-containing gene, just precedes the appearance of the first post-mitotic neurons. So far, its only reported function in the spinal cord is in specifying subsets of neurons. Here we address its possible function in controlling the balance between proliferation and commitment of neural progenitors. We report that increasing Pax6 level is sufficient to push neural progenitors toward cell cycle exit and neuronal commitment via Neurogenin 2 (Ngn2) upregulation. However, neuronal precursors maintaining Pax6(On) fail to perform neuronal differentiation. Conversely, turning off Pax6 function in these precursors is sufficient to provoke premature differentiation and the number of differentiated neurons depends of the amount of Pax6 protein. Moreover, we found that Pax6 expression involves negative feedback regulation by Ngn2 and this repression is critical for the proneural activity of Ngn2. We present a model in which the level of Pax6 activity first conditions the moment when a given progenitor will leave the cell cycle and second, the moment when a selected neuronal precursor will irreversibly differentiate. (c) 2007 Elsevier Inc. All rights reserved.