Expression of Phox2 transcription factors and induction of the dopaminergic phenotype in primary sensory neurons
Expression of Phox2 transcription factors and induction of the dopaminergic phenotype in primary sensory neurons
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DOI：
10.1006/mcne.2002.1135
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发表时间：
2002-07-01
影响因子：
3.5
通讯作者：
Katz, DM
中科院分区：
文献类型：
--
作者：
Brosenitsch, TA;Katz, DM
细胞类型特异性转录因子可以通过对相对非特异性的环境信号赋予选择性反应来调节表型多样性。为了验证这一假设，我们研究了同源结构域转录因子Phox 2a/2b是否在多巴胺能表型的活性依赖性表达中发挥作用，使用岩神经节（PG）：感觉神经元作为模型。Phox 2a/2b表达的时间与PG神经元表达多巴胺合成酶酪氨酸羟化酶（TH）的能力精确相关，以响应去极化刺激。Phox 2a/2b表达在胚胎第16.5天最高，此时几乎所有PG神经元均表现出活性依赖性TH诱导，随后福尔斯与活性依赖性TH诱导的丧失平行下降。然而，在所有多巴胺能神经元中保持表达。在体内，PG神经元的生理刺激仅在Phox 2a/2b（+）细胞中诱导TH表达。我们的数据表明，Phox 2a/2b的组成性表达定义的潜力，成为多巴胺能神经元在响应膜去极化过程中的一个关键窗口的表型可塑性。
Cell-type-specific transcription factors may regulate phenotypic diversity by conferring selective responsiveness to relatively nonspecific environmental cues. To test this hypothesis, we examined whether the homeodomain transcription factors Phox2a/2b play a role in activity-dependent expression of the dopaminergic phenotype using petrosal ganglion (PG) :sensory neurons as a model. The timing of Phox2a/2b expression is precisely correlated with the ability of PG neurons to express the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), in response to depolarizing stimuli. Phox2a/2b expression is highest at embryonic day 16.5, when virtually all PG neurons exhibit activity-dependent TH induction, and subsequently falls in parallel with the loss of activity-dependent TH induction. Expression is maintained, however, in all dopaminergic neurons. Physiologic stimulation of PG neurons in vivo induces TH expression exclusively in Phox2a/2b(+) cells. Our data suggest that constitutive expression of Phox2a/2b defines the potential of neurons to become dopaminergic in response to membrane depolarization during a critical window of phenotypic plasticity.