Dynamics of tyrosine hydroxylase promoter activity during midbrain dopaminergic neuron development
Dynamics of tyrosine hydroxylase promoter activity during midbrain dopaminergic neuron development
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DOI：
10.1046/j.1471-4159.2002.00972.x
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发表时间：
2002-07-01
影响因子：
4.7
通讯作者：
Kobayashi, K
中科院分区：
文献类型：
--
作者：
Matsushita, N;Okada, H;Kobayashi, K
腹侧中脑中产生多巴胺 (DA) 的神经元由特定的神经元谱系产生，并形成介导多种中枢神经系统功能的选择性轴突通路。酪氨酸羟化酶 (TH) 编码基因的表达是儿茶酚胺生物合成的关键酶，在中脑 DA 神经元的发育过程中受到调节。在本研究中，我们通过使用绿色荧光蛋白（GFP）报告系统报告了腹侧中脑TH基因启动子的发育调控和细胞类型特异性。产生的转基因小鼠在大鼠 TH 基因 9-kb 上游区域的控制下，在大多数中脑 DA 神经元中表达 GFP。在胚胎早期，在发育中的 DA 神经元中诱导 GFP 表达，然后在胚胎后期该表达显着下调。然而，在产后早期发育过程中，该表达被重新激活并接近成人水平。 GFP 表达模式的这些发育变化表明 DA 神经元发育过程中 TH 基因表达的多步调控机制的存在。 TH启动子似乎具有至少在早期胚胎阶段诱导TH表达及其在出生后发育过程中重新激活所必需的转录元件。
Dopamine (DA)-producing neurons in the ventral midbrain are generated from a specified neuronal lineage and form selective axonal pathways that mediate multiple CNS functions. Expression of the gene encoding tyrosine hydroxylase (TH), which is a key enzyme of catecholamine biosynthesis, is regulated during the development of midbrain DA neurons. In the present study, we report the developmental regulation and cell type specificity of TH gene promoter in the ventral midbrain by using a green fluorescent protein (GFP) reporter system. Transgenic mice were generated that express GFP in the majority of midbrain DA neurons under the control of the 9-kb upstream region of the rat TH gene. At an early embryonic stage, GFP expression was induced in the developing DA neurons, and the expression was then markedly down-regulated at later embryonic stages. However, the expression was reactivated and approached the adult levels during early post-natal development. These developmental changes in GFP expression patterns suggest the presence of multistep regulatory mechanisms for TH gene expression during DA neuron development. The TH promoter appears to possess transcriptional elements at least necessary for the induction of TH expression at the early embryonic stage and its reactivation during the post-natal development.