Tsarovina Konstantina, Pattyn Alexandre, Stubbusch Jutta, Müller Frank, van der Wees Jacqueline, Schneider Carolin, Brunet Jean-Francois, Rohrer Hermann
Max-Planck-Institut für Hirnforschung, Abteilung Neurochemie, Deutschordenstr. 46, 60528 Frankfurt/Main, Germany.
Development. 2004 Oct;131(19):4775-86. doi: 10.1242/dev.01370. Epub 2004 Aug 25.
Sympathetic neurons are specified during their development from neural crest precursors by a network of crossregulatory transcription factors, which includes Mash1, Phox2b, Hand2 and Phox2a. Here, we have studied the function of Gata2 and Gata3 zinc-finger transcription factors in autonomic neuron development. In the chick, Gata2 but not Gata3 is expressed in developing sympathetic precursor cells. Gata2 expression starts after Mash1, Phox2b, Hand2 and Phox2a expression, but before the onset of the noradrenergic marker genes Th and Dbh, and is maintained throughout development. Gata2 expression is affected in the chick embryo by Bmp gain- and loss-of-function experiments, and by overexpression of Phox2b, Phox2a, Hand2 and Mash1. Together with the lack of Gata2/3 expression in Phox2b knockout mice, these results characterize Gata2 as member of the Bmp-induced cluster of transcription factors. Loss-of-function experiments resulted in a strong reduction in the size of the sympathetic chain and in decreased Th expression. Ectopic expression of Gata2 in chick neural crest precursors elicited the generation of neurons with a non-autonomic, Th-negative phenotype. This implies a function for Gata factors in autonomic neuron differentiation, which, however, depends on co-regulators present in the sympathetic lineage. The present data establish Gata2 and Gata3 in the chick and mouse, respectively, as essential members of the transcription factor network controlling sympathetic neuron development.
交感神经元在从神经嵴前体发育的过程中，由一个交叉调节转录因子网络决定，该网络包括Mash1、Phox2b、Hand2和Phox2a。在此，我们研究了Gata2和Gata3锌指转录因子在自主神经元发育中的功能。在鸡胚中，Gata2而非Gata3在发育中的交感前体细胞中表达。Gata2的表达在Mash1、Phox2b、Hand2和Phox2a表达之后开始，但在去甲肾上腺素能标记基因Th和Dbh开始表达之前，并在整个发育过程中持续存在。通过Bmp功能获得和缺失实验以及Phox2b、Phox2a、Hand2和Mash1的过表达，鸡胚中的Gata2表达受到影响。连同Phox2b基因敲除小鼠中缺乏Gata2/3表达，这些结果将Gata2表征为Bmp诱导的转录因子簇的成员。功能缺失实验导致交感神经链大小显著减小以及Th表达降低。Gata2在鸡神经嵴前体中的异位表达引发了具有非自主、Th阴性表型的神经元的产生。这意味着Gata因子在自主神经元分化中具有功能，然而，这取决于交感神经谱系中存在的共调节因子。目前的数据分别在鸡和小鼠中确定了Gata2和Gata3是控制交感神经元发育的转录因子网络的重要成员。
