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首页> 外文期刊>The European Journal of Neuroscience >RARbeta isoform-specific regulation of DARPP-32 gene expression: an ectopic expression study in the developing rat telencephalon.
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RARbeta isoform-specific regulation of DARPP-32 gene expression: an ectopic expression study in the developing rat telencephalon.

机译：DARPP-32基因表达的RARbeta亚型特异性调节：在发育中的大鼠端脑的异位表达研究。

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Dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32) is a key molecule for dopamine neurotransmission. The molecular mechanisms underlying the regulation of DARPP-32 in the developing brain remains elusive. Previous studies have shown that retinoids are capable of inducing DARPP-32 in striatal cell culture, suggesting that retinoids are candidate molecules for controlling DARPP-32 expression. In the present study, we first studied the expression profiles of retinoid receptors and their associated co-factors in the developing rat telencephalon by RT-PCR. The results showed that among the retinoid receptors, RARbeta and RXRgamma were nearly selectively expressed in the developing striatum. By contrast, the retinoid receptors associated transcriptional co-factors, including the co-repressors of N-CoR and SMRT, and the co-activators of SRC-1 and P/CAF, were ubiquitously expressed in the developing telencephalon. In light of the previous findings that DARPP-32 was inducible by retinoids in striatal culture, but not in cortical culture, we hypothesized that the striatum-selective RARbeta and RXRgamma may mediate DARPP-32 induction by retinoids. To test this hypothesis, we used the gain-of-function approach to ectopically express RARbeta and RXRgamma in the developing cerebral cortex that lacked these two retinoid receptors. Ectopic expression of RARbeta1, but not RXRgamma1, up-regulated DARPP-32 in the cortical explant culture. Notably, DARPP-32 was up-regulated only by the RARbeta1 isoform, but not by other RARbeta isoforms. Our study suggests that RARbeta signaling may regulate DARPP-32 gene expression by an isoform-specific mechanism in developing telencephalic neurons. The molecular diversity of RARbeta isoforms may underlie parts of the complex gene regulation by retinoids during neural development.
机译：多巴胺和腺苷3'：5'-单磷酸调节的磷蛋白（DARPP-32）是多巴胺神经传递的关键分子。在发育中的大脑中调节DARPP-32的分子机制尚不清楚。先前的研究表明，类视黄醇能够在纹状体细胞培养物中诱导DARPP-32，这表明类视黄醇是控制DARPP-32表达的候选分子。在本研究中，我们首先通过RT-PCR研究了类维生素A受体及其相关辅因子在发育中的大鼠端脑的表达情况。结果表明，在类视黄醇受体中，RARbeta和RXRgamma在发育中的纹状体中几乎选择性表达。相比之下，类维生素A受体相关的转录辅因子，包括N-CoR和SMRT的共阻遏物，以及SRC-1和P / CAF的共激活因子，在发育中的端脑中普遍表达。鉴于先前的发现，纹状体培养中类视黄醇可诱导DARPP-32，而皮层培养中不能诱导类视黄醇，因此我们假设纹状体选择性RARbeta和RXRgamma可能介导类视黄醇对DARPP-32的诱导。为了验证这一假设，我们使用功能获得方法在缺乏这两种类维生素A受体的发育中大脑皮层中异位表达RARbeta和RXRgamma。 RARbeta1，而不是RXRgamma1，在皮质外植体培养物中的异位表达上调了DARPP-32。值得注意的是，DARPP-32仅由RARbeta1亚型上调，而不受其他RARbeta亚型上调。我们的研究表明RARbeta信号传导可能通过发育中的脑神经元的一种亚型特异性机制调节DARPP-32基因的表达。 RARbeta亚型的分子多样性可能是神经发育过程中类视黄醇对复杂基因调控的部分基础。

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