Research Group Developmental Neurobiology, Max-Planck-Institute for Brain Research, 60528 Frankfurt/M, Germany.
J Neurosci. 2010 Aug 11;30(32):10833-43. doi: 10.1523/JNEUROSCI.0175-10.2010.
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-xL, and NFkappaB) 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.
转录因子 Gata3 对于交感神经元和肾上腺嗜铬细胞的发育至关重要。由于 Gata3 的表达一直维持到成年期,因此我们通过条件性 Gata3 缺失来研究其在胚胎期和成年期分化的交感肾上腺细胞中的功能。在胚胎期表达 DBH 的神经元中 Gata3 的失活会由于细胞凋亡和增殖减少而导致神经元数量的强烈减少。未观察到对去甲肾上腺素能基因表达(TH 和 DBH)的选择性影响。有趣的是,成年动物中表达 DBH 的神经元中 Gata3 的消除也导致几乎完全丧失交感神经元。在 Gata3 缺陷型群体中,抗凋亡基因(Bcl-2、Bcl-xL 和 NFkappaB)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,Gata3 一直需要维持交感神经元谱系中的存活,但不会影响到成年动物的成熟神经元的分化。