Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells
Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells
复制标题
DOI：
10.1016/s0896-6273(00)80729-1
复制
发表时间：
1999-04-01
期刊：
影响因子：
16.2
通讯作者：
Anderson, DJ
中科院分区：
文献类型：
--
作者：
Lo, LC;Morin, X;Anderson, DJ
我们已经调查了规格的去甲肾上腺素能神经递质的身份在神经嵴干细胞（NCSC）。配对同源结构域转录因子Phox 2a的野生型和显性阴性形式的逆转录病毒表达表明该蛋白（和/或密切相关的Phox 2b）在这些细胞中内源性酪氨酸羟化酶（TH）和多巴胺-β羟化酶（DBH）基因表达的调节中具有重要和直接的作用。与cAMP合作，Phox 2a可以诱导TH的表达，但不能诱导DBH或泛神经元基因的表达。此外，Phox 2蛋白是骨形态发生蛋白2（BMP 2）（其诱导Phox 2a/B）和毛喉素诱导TH和DBH所必需的。它们也是神经元分化所必需的。这些数据表明，Phox 2a/B协调规范的神经递质的身份和神经元的命运，通过合作的环境信号在交感神经母细胞。
We have investigated the specification of noradrenergic neurotransmitter identity in neural crest stem cells (NCSCs). Retroviral expression of both wild-type and dominant-negative forms of the paired homeodomain transcription factor Phox2a indicates a crucial and direct role for this protein (and/or the closely related Phox2b) in the regulation of endogenous tyrosine hydroxylase (TH) and dopamine-beta hydroxylase (DBH) gene expression in these cells. In collaboration with cAMP, Phox2a can induce expression of TH but not of DBH or of panneuronal genes. Phox2 proteins are, moreover, necessary for the induction of both TH and DBH by bone morphogenetic protein 2 (BMP2) (which induces Phox2a/b) and forskolin. They are also necessary for neuronal differentiation. These data suggest that Phox2a/b coordinates the specification of neurotransmitter identity and neuronal fate by cooperating environmental signals in sympathetic neuroblasts.