Regulated Expression of ATF5 Is Required for the Progression of Neural Progenitor Cells to Neurons
Regulated Expression of ATF5 Is Required for the Progression of Neural Progenitor Cells to Neurons
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DOI：
10.1523/jneurosci.23-11-04590.2003
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发表时间：
2003-06
期刊：
影响因子：
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通讯作者：
J. Angelastro;T. Ignatova;V. Kukekov;D. Steindler;George B Stengren;C. Mendelsohn;L. Greene
中科院分区：
文献类型：
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作者：
J. Angelastro;T. Ignatova;V. Kukekov;D. Steindler;George B Stengren;C. Mendelsohn;L. Greene
脑发育的一个重要里程碑是神经祖细胞向有丝分裂后神经元的转变。我们报告说，bZIP转录因子ATF 5在这一过程中起着重要的调节作用。在发育中的脑中，在含有神经干细胞和祖细胞的脑室区中，ATF 5表达较高，并且在有丝分裂后的神经元中检测不到。在附着的克隆神经球培养物中，ATF 5由神经干/祖细胞表达，并且在tau阳性神经元中检测不到。在PC 12细胞培养中，神经生长因子（NGF）显著下调内源性ATF 5蛋白和转录，而外源性ATF 5抑制NGF促进的神经突生长。这种抑制需要CRE位点的抑制。相反，显性负性ATF 5的功能丧失加速了NGF促进的轴突发生。外源性ATF 5也抑制，和显性负性ATF 5和小干扰RNA针对ATF 5促进，通过培养nestin阳性端脑细胞的神经发生。这些发现表明，ATF 5阻断神经祖细胞分化为神经元，并且必须下调以允许该过程发生。
An important milestone in brain development is the transition of neuroprogenitor cells to postmitotic neurons. We report that the bZIP transcription factor ATF5 plays a major regulatory role in this process. In developing brain ATF5 expression is high within ventricular zones containing neural stem and progenitor cells and is undetectable in postmitotic neurons. In attached clonal neurosphere cultures ATF5 is expressed by neural stem/progenitor cells and is undetectable in tau-positive neurons. In PC12 cell cultures nerve growth factor (NGF) dramatically downregulates endogenous ATF5 protein and transcripts, whereas exogenous ATF5 suppresses NGF-promoted neurite outgrowth. Such inhibition requires the repression of CRE sites. In contrast, loss of function conferred by dominant-negative ATF5 accelerates NGF-promoted neuritogenesis. Exogenous ATF5 also suppresses, and dominant-negative ATF5 and a small-interfering RNA targeted to ATF5 promote, neurogenesis by cultured nestin-positive telencephalic cells. These findings indicate that ATF5 blocks the differentiation of neuroprogenitor cells into neurons and must be downregulated to permit this process to occur.