The Gata3 Transcription Factor Is Required for the Survival of Embryonic and Adult Sympathetic Neurons
The Gata3 Transcription Factor Is Required for the Survival of Embryonic and Adult Sympathetic Neurons
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DOI：
10.1523/jneurosci.0175-10.2010
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发表时间：
2010-08-11
影响因子：
5.3
通讯作者：
Rohrer, Hermann
中科院分区：
文献类型：
--
作者：
Tsarovina, Konstantina;Reiff, Tobias;Rohrer, Hermann
转录因子Gata 3对交感神经元和肾上腺嗜铬细胞的发育至关重要。由于Gata 3的表达一直维持到成年阶段，我们通过条件性Gata 3消除来解决其在胚胎和成年阶段分化的交感肾上腺细胞中的功能。Gata 3在胚胎DBH表达神经元中的失活导致神经元数量的强烈减少，这是由于凋亡性细胞死亡和增殖减少。未观察到对去甲肾上腺素能基因表达（TH和DBH）的选择性作用。有趣的是，成年动物的DBH表达神经元中的Gata 3消除也导致交感神经元几乎完全丧失。在Gata 3缺陷群体中，抗凋亡基因（Bcl-2、Bcl-x（L）和NF κ B）的表达减少，而促凋亡基因（Bik、Bok和Bmf）的表达增加。去甲肾上腺素能基因（TH和DBH）的表达不受影响。这些结果表明，Gata 3是维持存活所持续需要的，而不是在交感神经元谱系中分化成成年动物的成熟神经元。
The transcription factor Gata3 is essential for the development of sympathetic neurons and adrenal chromaffin cells. As Gata3 expression is maintained up to the adult stage, we addressed its function in differentiated sympathoadrenal cells at embryonic and adult stages by conditional Gata3 elimination. Inactivation of Gata3 in embryonic DBH-expressing neurons elicits a strong reduction in neuron numbers due to apoptotic cell death and reduced proliferation. No selective effect on noradrenergic gene expression (TH and DBH) was observed. Interestingly, Gata3 elimination in DBH-expressing neurons of adult animals also results in a virtually complete loss of sympathetic neurons. In the Gata3-deficient population, the expression of anti-apoptotic genes (Bcl-2, Bcl-x(L), and NF kappa B) is diminished, whereas the expression of pro-apoptotic genes (Bik, Bok, and Bmf) was increased. The expression of noradrenergic genes (TH and DBH) is not affected. These results demonstrate that Gata3 is continuously required for maintaining survival but not differentiation in the sympathetic neuron lineage up to mature neurons of adult animals.